WO2025117869A1

WO2025117869A1 - Methods of treating recurrent ovarian cancer and endometrial cancer with bispecific anti-muc16 x anti-cd28 antibodies in combination with anti-pd-1 antibodies or bispecific anti-muc16 x anti-cd3 antibodies

Info

Publication number: WO2025117869A1
Application number: PCT/US2024/057927
Authority: WO
Inventors: Thomas Smith ULDRICK JR.; Elizabeth Miller; Israel Lowy
Original assignee: Regeneron Pharmaceuticals Inc
Current assignee: Regeneron Pharmaceuticals Inc
Priority date: 2023-11-29
Filing date: 2024-11-28
Publication date: 2025-06-05
Anticipated expiration: 2026-05-29

Abstract

The present disclosure provides methods for treating, reducing the severity, or inhibiting the growth of a MUC16-expressing cancer (e.g., ovarian cancer or endometrial cancer). In certain embodiments, the methods of the present disclosure comprise administering to a subject in need thereof a therapeutically effective amount of a bispecific antibody or antigen-binding fragment thereof that specifically binds mucin 16 (MUC16) and CD28 in combination with an antibody or antigen-binding fragment thereof that specifically binds to programmed death 1 (PD-1) receptor or a bispecific antibody or antigen-binding fragment thereof that specifically binds MUC16 and CD3.

Description

METHODS OF TREATING RECURRENT OVARIAN CANCER AND ENDOMETRIAL CANCER WITH BISPECIFIC ANTI-MUC16 X ANTI-CD28 ANTIBODIES IN COMBINATION WITH ANTI-PD- 1 ANTIBODIES OR BISPECIFIC ANTI-MUC16 X ANTI-CD3 ANTIBODIES REFERENCE TO A SEQUENCE LISTING [0001] This application incorporates by reference a computer readable Sequence Listing in ST.26 XML format, titled 11049WO01_Sequence, created on November 18, 2024 and containing 74,648 bytes. FIELD OF THE INVENTION [0002] The present disclosure relates to methods for treating cancer comprising administering to a subject in need thereof a therapeutically effective amount of a bispecific antibody that specifically binds to mucin 16 (MUC16) and CD28 in combination with an antibody that specifically binds to programmed death 1 (PD-1) receptor, or a bispecific antibody that specifically binds to MUC16 and CD3. BACKGROUND [0003] Mucin 16 (MUC16), also known as cancer antigen 125, carcinoma antigen 125, carbohydrate antigen 125, or CA-125, is a single transmembrane domain highly glycosylated integral membrane glycoprotein that is highly expressed in ovarian cancer. MUC16 consists of three major domains: an extracellular N-terminal domain, a large tandem repeat domain interspersed with sea urchin sperm, enterokinase, and agrin (SEA) domains, and a carboxyl terminal domain that comprises a segment of the transmembrane region and a short cytoplasmic tail. Proteolytic cleavage results in shedding of the extracellular portion of MUC16 into the bloodstream. MUC16 is overexpressed in cancers including ovarian cancer, breast cancer, pancreatic cancer, non-small-cell lung cancer, intrahepatic cholangiocarcinoma-mass forming type, adenocarcinoma of the uterine cervix, and adenocarcinoma of the gastric tract, and in diseases and conditions including inflammatory bowel disease, liver cirrhosis, cardiac failure, peritoneal infection, and abdominal surgery. (Haridas, D. et al., 2014, FASEB J., 28:4183-4199). Expression on cancer cells is shown to protect tumor cells from the immune system. (Felder, M. et al., 2014, Molecular Cancer, 13:129) Methods for treating ovarian cancer using antibodies to MUC16 have been investigated. Oregovomab and abgovomab are anti-MUC16 antibodies which have had limited success. (Felder, supra, Das, S. and Batra, S.K.2015, Cancer Res.75:4660-4674.) [0004] CD28 is a type I transmembrane protein, which has a single extracellular Ig-V-like domain assembled as a homodimer and which is expressed on the surface of T cells. CD28 is the receptor for the CD80 (B7.1) and CD86 (B7.2) proteins and is activated by CD80 or CD86 expressed on antigen-presenting cells (APCs). The binding of CD28 to CD80 or CD86 provides co-stimulatory signals important for T cell activation and survival. T cell stimulation through CD28, in addition to the T-cell receptor (TCR), provides a potent signal for the production of various interleukins. CD28 also potentiates cellular signals such as pathways controlled by the NFκB transcription factor after TCR activation. The CD28 co-signal is important for effective T-cell activation such as T cell differentiation, proliferation, cytokine release and cell-death. Anti-CD28 antibodies have been proposed for therapeutic purposes involving the activation of T cells. One particular anti-CD28 antibody, TGN1412 (anti-CD28 superagonist), was used in a clinical trial in 2006, in which six healthy volunteers were dosed intravenously with TGN1412 (anti-CD28 superagonist) at a dose of 0.1 mg/kg. Within two hours, all six patients had significant inflammatory responses (cytokine storm), and all patients were in multi-organ failure within sixteen hours. Subjects were treated with corticosteroids, and cytokine levels returned to normal within 2-3 days (Suntharalingam, et al., Cytokine Storm in a Phase 1 Trial of the Anti-CD28 Monoclonal Antibody TGN1412, NEJM 355:1018-1028 (2006)). [0005] CD3 is a homodimeric or heterodimeric antigen expressed on T cells in association with the T cell receptor complex (TCR) and is required for T cell activation. Functional CD3 is formed from the dimeric association of two of four different chains: epsilon, zeta, delta and gamma. The CD3 dimeric arrangements include gamma/epsilon, delta/epsilon and zeta/zeta. Antibodies against CD3 have been shown to cluster CD3 on T cells, thereby causing T cell activation in a manner similar to the engagement of the TCR by peptide-loaded MHC molecules. Anti-CD3 antibodies have been proposed for therapeutic purposes involving the activation of T cells. In addition, bispecific antibodies that are capable of binding CD3 and a target antigen have been proposed for therapeutic uses involving targeting T cell immune responses to tissues and cells expressing the target antigen. [0006] Programmed death-1 (PD-1) receptor signaling in the tumor microenvironment plays a key role in allowing tumor cells to escape immune surveillance by the host immune system. Blockade of the PD-1 signaling pathway has demonstrated clinical activity in patients with multiple tumor types, and antibody therapeutics that block PD-1 (e.g., nivolumab and pembrolizumab) have been approved for the treatment of metastatic melanoma and metastatic squamous non-small cell lung cancer. Recent data has demonstrated the clinical activity of PD-1 blockade in patients with aggressive NHL and Hodgkin's lymphoma (Lesokhin, et al.2014, Abstract 291, 56th ASH Annual Meeting and Exposition, San Francisco, Calif.; Ansell et al.2015, N. Engl. J. Med.372(4):311-9). [0007] Ovarian cancer is the most lethal of the gynecologic malignancies; although the estimated number of new cases of ovarian cancer among American women are much lower than certain other cancers, the death-to-incidence ratio for ovarian cancer is considerably higher (Siegal et al., CA Cancer J Clin 66:7-30, 2016). Ovarian cancer is frequently diagnosed at an advanced stage, which contributes to its lethality. The current standard of care for ovarian cancer is surgery followed by chemotherapy, namely a combination of platinum agents and taxanes. Whilst the majority of patients respond to initial treatment, most experience a recurrence of the disease, resulting in a cycle of repeated surgeries and additional rounds of chemotherapy. Although recurrent ovarian cancers may respond to further treatment, virtually all of them will ultimately become resistant to currently available therapies. Despite recent advances in therapy such as PARP inhibitors for patients carrying BRCA or other homologous recombination deficiency (HRD) mutations, advanced ovarian cancer remains a disease of high unmet need. [0008] Evidence suggests that ovarian cancer may be amenable to some forms of immunotherapy (Kandalaft et al., J. Clin. Oncol., 29:925-933, 2011). For example, ovarian cancer patients whose tumors were positive for intraepithelial CD8⁺ T lymphocyte infiltration had significantly better overall and progression-free survival than patients without intraepithelial CD8⁺ T lymphocyte infiltration (Hamanishi et al., PNAS, 104:3360-65, 2007; and Zhang et al., N. Engl. J. Med., 348:203-213, 2003). Moreover, some patients have shown spontaneous immune response to their tumors, demonstrated by detection of tumor-reactive T cells and antibodies in the blood, tumor or ascites of patients with advanced disease (Schliengar et al., Clin Cancer Res, 9:1517-1527, 2003). Blockade of the PD-1/ PD-L1 checkpoint pathway has shown some benefit in ovarian cancer; PD-1 blockade monotherapy resulted in an overall response rate (ORR) of approximately 10-15% in early clinical trials (Hamanishi et al., supra). However, blockade of this pathway alone is clearly not sufficient. [0009] MUC16 is also expressed in endometrial cancer. In a small series of 12 cases of endometrial cancers detailed in the Human Protein Atlas, 75% of cases expressed MUC16 in 25% of cells. A similar MUC16 prevalence was observed in a 485-person evaluation of endometrial cancer at time of resection of the uterus (Kakimoto et al., Diagnostic Pathology, 16:28, 2021). These data are also consistent with in-house evaluation of MUC16 prevalence, with an estimated 73% of cases having ≥25% of tumor cells that stain positive for MUC16 by immunohistochemistry. [0010] Until recently, the standard-of-care first line therapy for women with advanced endometrial cancer, including cancer that has progressed after surgery +/- radiation, has been carboplatin + paclitaxel based on a study that showed non-inferior overall survival with this regimen compared to the more toxic regimen of doxorubicin, cisplatin and paclitaxel (Miller et al., Journal of Clinical Oncology, 38(33):3841-3850, 2020). There are two FDA approved anti-PD1 antibodies, pembrolizumab and dostarlimab, for second line treatment in patients with DNA mismatch repair deficient (dMMR) endometrial cancer, which comprises about 25% of endometrial cancer cases (Lorenzi et al., Journal of Oncology, Article ID 1807929, 2020). The overall response rate with anti- PD-1 in this setting is approximately 45% with responses being durable in a majority of patients. For patients with pMMR (mismatch repair proficient) or not microsatellite instability (MSI)-High advanced endometrial cancer, the combination of pembrolizumab and lenvatinib was FDA approved in 2022 based on demonstration of improved progression-free survival (PFS) compared to chemotherapy (Makker et al, New England Journal of Medicine, 386:437-448, 2022). Recently, results of two randomized phase 3 studies demonstrated in the first-line setting for advanced or recurrent advanced endometrial cancer, anti-PD-1 therapy with pembrolizumab or dostarlimab added to carboplatin and paclitaxel lead to significant improvement in PFS, especially in women with dMMR endometrial cancer. Given the potential for anti-PD-1 therapy earlier in treatment, there is an emerging need for 2+ line therapy after anti-PD-1 therapy in women with advanced endometrial cancer. [0011] In view of the high unmet need, additional therapies for targeting ovarian cancers and endometrial cancers are needed. BRIEF SUMMARY OF THE INVENTION [0012] According to certain embodiments, the present disclosure provides methods for treating, ameliorating at least one symptom or indication, or inhibiting the growth of a MUC16-expressing cancer in a subject. The methods according to this aspect of the disclosure comprise administering a therapeutically effective amount of a bispecific antibody that specifically binds to mucin 16 (MUC16) and CD28 in combination with an antibody or antigen-binding fragment thereof that specifically binds to programmed death 1 (PD-1), or a bispecific antibody that specifically binds to MUC16 and CD3, to a subject in need thereof. [0013] In certain embodiments of the present disclosure, methods are provided for treating, ameliorating at least one symptom or indication, or inhibiting the growth of a MUC16-expressing cancer in a subject. In certain embodiments of the present disclosure, methods are provided for delaying the growth of a tumor or preventing tumor recurrence. The methods, according to this and other aspects of the disclosure, comprise sequentially administering one or more doses of a therapeutically effective amount of a bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment thereof in combination with one or more doses of a therapeutically effective amount of an anti-PD-1 antibody or antigen-binding fragment thereof, or a bispecific anti-MUC16 x anti-CD3 antibody or antigen-binding fragment thereof, to a subject in need thereof. [0014] In one aspect, the present disclosure provides a method of treating a MUC16-expressing cancer in a subject in need thereof, comprising administering to the subject a combination of a bispecific antibody or antigen-binding fragment thereof comprising a first antigen-binding domain that specifically binds mucin 16 (MUC16), and a second antigen-binding domain that specifically binds human CD28, and an antibody or antigen-binding fragment thereof that specifically binds programmed death 1 (PD-1) receptor, wherein the anti-MUC16 x anti-CD28 bispecific antibody is administered to the subject at a dose of at least 0.1 mg. [0015] In some embodiments, the anti-PD-1 antibody or antigen-binding fragment comprises: (a) three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) contained within a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 51; and (b) three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) contained within a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 55. In some cases, the anti-PD-1 antibody or antigen-binding fragment comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 52, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 53, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 54. In some cases, the anti-PD-1 antibody or antigen-binding fragment comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 56, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 57, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 58. [0016] In some embodiments, the anti-PD-1 antibody or antigen-binding fragment comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 51, and a LCVR comprising the amino acid sequence of SEQ ID NO: 55. [0017] In some embodiments, the anti-PD-1 antibody or antigen-binding fragment is an anti-PD-1 antibody comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 59 and a light chain comprising the amino acid sequence of SEQ ID NO: 60. [0018] In some embodiments, the anti-PD-1 antibody or antigen-binding fragment is administered to the subject at a dose of from 300 to 400 mg once every three weeks. In some cases, the anti- PD-1 antibody is administered to the subject at a dose of 350 mg once every three weeks. In some cases, the anti-PD-1 antibody is cemiplimab. [0019] In some embodiments, the bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment is administered at a dose of 0.1 mg, 0.3 mg, 1 mg, 3 mg, 10 mg, 30 mg, 100 mg, 300 mg, or 1000 mg once weekly during the course of a dosing regimen. [0020] In one aspect, the present disclosure provides a method of treating a MUC16-expressing cancer in a subject in need thereof, comprising administering to the subject a combination of a bispecific antibody or antigen-binding fragment thereof comprising a first antigen-binding domain that specifically binds mucin 16 (MUC16), and a second antigen-binding domain that specifically binds human CD28, and a bispecific antibody or antigen-binding fragment thereof comprising a first antigen-binding domain that specifically binds mucin 16 (MUC16), and a second antigen-binding domain that specifically binds human CD3, wherein the anti-MUC16 x anti-CD28 bispecific antibody or antigen-binding fragment is administered to the subject at a dose of at least 0.03 mg. [0021] In some embodiments the first antigen-binding domain of the anti-MUC16 x anti-CD3 antibody or antigen-binding fragment comprises: (a) three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) contained within a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 31; and (b) three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) contained within a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 43. In some cases, the first antigen-binding domain of the anti-MUC16 x anti-CD3 antibody or antigen-binding fragment comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 32, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 33, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 34. In some cases, the first antigen-binding domain of the anti-MUC16 x anti-CD3 antibody or antigen-binding fragment comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 44, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 45, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 46. [0022] In some embodiments, the first antigen-binding domain of the anti-MUC16 x anti-CD3 antibody or antigen-binding fragment comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 31, and a LCVR comprising the amino acid sequence of SEQ ID NO: 43. [0023] In some embodiments, the second antigen-binding domain of the anti-MUC16 x anti-CD3 antibody or antigen-binding fragment comprises: (a) three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) contained within a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 35; and (b) three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) contained within a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 43. In some cases, the second antigen-binding domain of the anti-MUC16 x anti-CD3 antibody or antigen-binding fragment comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 36, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 37, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 38. In some cases, the second antigen-binding domain of the anti-MUC16 x anti-CD3 antibody or antigen-binding fragment comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 44, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 45, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 46. [0024] In some embodiments, the second antigen-binding domain of the anti-MUC16 x anti-CD3 antibody or antigen-binding fragment comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 35, and a LCVR comprising the amino acid sequence of SEQ ID NO: 43. [0025] In some embodiments, the second antigen-binding domain of the anti-MUC16 x anti-CD3 antibody or antigen-binding fragment comprises: (a) three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) contained within a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 39; and (b) three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) contained within a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 43. In some cases, the second antigen-binding domain of the anti-MUC16 x anti-CD3 antibody or antigen-binding fragment comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 40, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 41, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 42. In some cases, the second antigen-binding domain of the anti-MUC16 x anti-CD3 antibody or antigen-binding fragment comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 44, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 45, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 46. [0026] In some embodiments, the second antigen-binding domain of the anti-MUC16 x anti-CD3 antibody or antigen-binding fragment comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 39, and a LCVR comprising the amino acid sequence of SEQ ID NO: 43. [0027] In some embodiments, the anti-MUC16 x anti-CD3 antibody comprises a human IgG heavy chain constant region. In some cases, the human IgG heavy chain constant region is isotype IgG1. In some cases, the human IgG heavy chain constant region is isotype IgG4. [0028] In some embodiments, the anti-MUC16 x anti-CD3 antibody comprises a chimeric hinge that reduces Fcɣ receptor binding relative to a wild-type hinge of the same isotype. [0029] In some embodiments, the first heavy chain or the second heavy chain of the anti-MUC16 x anti-CD3 antibody, but not both, comprises a CH3 domain comprising a H435R (EU numbering) modification and a Y436F (EU numbering) modification. [0030] In some embodiments, the anti-MUC16 x anti-CD3 antibody comprises a first heavy chain comprising the amino acid sequence of SEQ ID NO: 47. In some embodiments, the anti-MUC16 x anti-CD3 antibody comprises a second heavy chain comprising the amino acid sequence of SEQ ID NO: 48. In some embodiments, the anti-MUC16 x anti-CD3 antibody comprises a second heavy chain comprising the amino acid sequence of SEQ ID NO: 49. In some embodiments, the anti- MUC16 x anti-CD3 antibody comprises a first heavy chain comprising the amino acid sequence of SEQ ID NO: 47, a second heavy chain comprising the amino acid sequence of SEQ ID NO: 48, and a common light chain comprising the amino acid sequence of SEQ ID NO: 50. In some embodiments, the anti-MUC16 x anti-CD3 antibody comprises a first heavy chain comprising the amino acid sequence of SEQ ID NO: 47, a second heavy chain comprising the amino acid sequence of SEQ ID NO: 49, and a common light chain comprising the amino acid sequence of SEQ ID NO: 50. In some cases, the anti-MUC16 x anti-CD3 antibody is REGN4018. [0031] In some embodiments, the anti-MUC16 x anti-CD3 antibody is administered to the subject at a dose of from 0.01 mg to 1000 mg weekly. In some cases, the anti-MUC16 x anti-CD3 antibody is administered to the subject at a dose of from 1 mg to 250 mg weekly. [0032] In some embodiments, the anti-MUC16 x anti-CD3 antibody or antigen-binding fragment is administered to the subject weekly for at least one week prior to administration of the anti-MUC16 x anti-CD28 antibody or antigen-binding fragment. In some cases, the anti-MUC16 x anti-CD3 antibody or antigen-binding fragment is administered to the subject weekly for four weeks or at least four weeks prior to administration of the anti-MUC16 x anti-CD28 antibody or antigen-binding fragment. In some cases, the anti-MUC16 x anti-CD3 antibody or antigen-binding fragment is administered to the subject weekly for five weeks or at least five weeks prior to administration of the anti-MUC16 x anti-CD28 antibody or antigen-binding fragment. [0033] In some embodiments, the anti-MUC16 x anti-CD3 antibody or antigen-binding fragment is administered weekly in a dosing regimen at a dose of 1 mg during week 1, at a dose of 20 mg during week 2, and at a dose of from 20 mg to 250 mg or 20 mg to 1000 mg during each subsequent week of the dosing regimen. In some cases, the anti-MUC16 x anti-CD3 antibody is administered to the subject as a split dose, optionally wherein the split dose is administered during week 1, or during week 1 and week 2, of a dosing regimen. In some embodiments, the bispecific anti-MUC16 x anti-CD3 antibody is administered to the subject at a dose of 1 mg during week 1, at a dose of 20 mg during week 2, wherein the dose of 20 mg is split into two equal doses of 10 mg administered to the subject on two days during week 2, and at a dose of 250 mg or up to 1000 mg during each subsequent week of the dosing regimen. In some embodiments, an anti-IL-6R antibody is prophylactically administered prior to administration of the bispecific anti-MUC16 x anti- CD3 antibody or antigen-binding fragment thereof. [0034] In any of the various embodiments discussed above, the MUC16-expressing cancer may be ovarian cancer, fallopian tube cancer, endometrial cancer, or primary peritoneal cancer. In some cases, the MUC16-expressing cancer is resistant to platinum-based chemotherapy. [0035] In any of the various embodiments discussed above, the subject may have previously been treated with a platinum-based chemotherapy. In any of the various embodiments discussed above, the subject may have previously been treated with anti-PD-1 therapy. [0036] In any of the various embodiments discussed above, the subject has an elevated serum CA-125 level prior to treatment with the methods discussed herein. In some embodiments, the subject has a serum CA-125 level at least two times the upper limit of normal prior to treatment with the anti-MUC16 x anti-CD28 antibody in combination with the anti-PD-1 antibody or anti-MUC16 x antiCD3 antibody. In some embodiments, the subject may have a serum CA-125 level of greater than 70 U/ml prior to treatment with the anti-MUC16 x anti-CD28 antibody in combination with the anti-PD-1 antibody or anti-MUC16 x antiCD3 antibody. [0037] In various embodiments, the first antigen-binding domain of the anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises: (a) three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) contained within a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 1; and (b) three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) contained within a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 9. In some cases, the first antigen-binding domain of the anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 2, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 3, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 4. In some cases, the first antigen-binding domain of the anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 10, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 11, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 12. [0038] In some embodiments, the first antigen-binding domain of the anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 1, and a LCVR comprising the amino acid sequence of SEQ ID NO: 9. [0039] In some embodiments, the second antigen-binding domain of the anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises: (a) three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) contained within a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 5; and (b) three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) contained within a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 9. In some cases, the second antigen-binding domain of the anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 6, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 8. In some cases, the second antigen-binding domain of the anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 10, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 11, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 12. [0040] In some embodiments, the second antigen-binding domain of the anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 5, and a LCVR comprising the amino acid sequence of SEQ ID NO: 9. [0041] In some embodiments, the anti-MUC16 x anti-CD28 antibody comprises a human IgG heavy chain constant region. In some cases, the human IgG heavy chain constant region is isotype IgG1. In some cases, the human IgG heavy chain constant region is isotype IgG4. [0042] In some embodiments, the anti-MUC16 x anti-CD28 antibody comprises a chimeric hinge that reduces Fcɣ receptor binding relative to a wild-type hinge of the same isotype. [0043] In some embodiments, the first heavy chain or the second heavy chain of the anti-MUC16 x anti-CD28 antibody, but not both, comprises a CH3 domain comprising a H435R (EU numbering) modification and a Y436F (EU numbering) modification. [0044] In some embodiments, the anti-MUC16 x anti-CD28 antibody comprises a first heavy chain comprising the amino acid sequence of SEQ ID NO: 13. In some embodiments, the anti-MUC16 x anti-CD28 antibody comprises a second heavy chain comprising the amino acid sequence of SEQ ID NO: 14. In some embodiments, the anti-MUC16 x anti-CD28 antibody comprises a first heavy chain comprising the amino acid sequence of SEQ ID NO: 13, a second heavy chain comprising the amino acid sequence of SEQ ID NO: 14, and a common light chain comprising the amino acid sequence of SEQ ID NO: 15. [0045] In some embodiments, the first antigen-binding domain of the anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises: (a) three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) contained within a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 16; and (b) three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) contained within a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 24. In some cases, the first antigen-binding domain of the anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 18, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 19. In some cases, the first antigen-binding domain of the anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 25, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 26, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 27. [0046] In some embodiments,the first antigen-binding domain of the anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 16, and a LCVR comprising the amino acid sequence of SEQ ID NO: 24. [0047] In some embodiments, the second antigen-binding domain of the anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises: (a) three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) contained within a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 20; and (b) three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) contained within a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 24. In some cases, the second antigen-binding domain of the anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 21, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 22, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 23. In some cases, the second antigen-binding domain of the anti- MUC16 x anti-CD28 antibody or antigen-binding fragment comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 25, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 26, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 27. [0048] In some embodiments, the second antigen-binding domain of the anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 20, and a LCVR comprising the amino acid sequence of SEQ ID NO: 24. [0049] In some embodiments, the anti-MUC16 x anti-CD28 antibody comprises a human IgG heavy chain constant region. In some cases, the human IgG heavy chain constant region is isotype IgG1. In some cases, the human IgG heavy chain constant region is isotype IgG4. [0050] In some embodiments, the anti-MUC16 x anti-CD28 antibody comprises a chimeric hinge that reduces Fcɣ receptor binding relative to a wild-type hinge of the same isotype. [0051] In some embodiments, the first heavy chain or the second heavy chain of the anti-MUC16 x anti-CD28 antibody, but not both, comprises a CH3 domain comprising a H435R (EU numbering) modification and a Y436F (EU numbering) modification. [0052] In some embodiments, the anti-MUC16 x anti-CD28 antibody comprises a first heavy chain comprising the amino acid sequence of SEQ ID NO: 28. In some embodiments, the anti-MUC16 x anti-CD28 antibody comprises a second heavy chain comprising the amino acid sequence of SEQ ID NO: 29. In some embodiments, the anti-MUC16 x anti-CD28 antibody comprises a first heavy chain comprising the amino acid sequence of SEQ ID NO: 28, a second heavy chain comprising the amino acid sequence of SEQ ID NO: 29, and a common light chain comprising the amino acid sequence of SEQ ID NO: 30. In some cases, the anti-MUC16 x anti-CD28 antibody is REGN5668. [0053] In any of the various embodiments, the anti-MUC16 x anti-CD28 antibody is administered to the subject at a dose of from 0.01 mg to 1000 mg weekly. In some cases, the anti-MUC16 x anti- CD3 antibody is administered to the subject at a dose of from 0.03 mg to 1000 mg weekly. [0054] In any of the various embodiments, the bispecific anti-MUC16 x anti-CD3 antibody or antigen-binding fragment is administered weekly in a dosing regimen at a dose of 0.1 mg, 0.3 mg, 1 mg, 3 mg, 10 mg, 30 mg, 100 mg, 300 mg, or 1000 mg. In any of the various embodiments, the bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment is administered weekly in a dosing regimen at a dose of 0.03 mg, 0.1 mg or 0.3 mg during week 5, and at a dose of 0.03 mg, 0.1 mg, 0.3 mg, 1 mg, 10 mg, 100 mg, 300 mg, or 1000 mg during each subsequent week of the dosing regimen. [0055] In any of the various embodiments discussed above or herein, the subject has stable disease, a partial response, or a complete response following administration of the anti-MUC16 x anti-CD28 antibody for at least one week at a dose of from 0.03 mg to 300 mg, or at a dose of from 0.03 mg to 1000 mg, in combination with the anti-PD-1 antibody or the anti-MUC16 x anti-CD3 antibody. [0056] The present disclosure also encompasses the use of the bispecific antibodies (MUC16 x CD28 and MUC16 x CD3) and/or the anti-PD-1 antibodies in the manufacture of a medicament for treating a MUC16-expressing cancer as set forth in any of the embodiments of the methods discussed above or herein. The present disclosure also encompasses bispecific antibodies (MUC16 x CD28 and MUC16 x CD3) and/or anti-PD-1 antibodies for use in any of the embodiments of the methods discussed above or herein. The present disclosure also encompasses pharmaceutical compositions comprising the bispecific antibodies (MUC16 x CD28 and MUC16 x CD3) and/or anti-PD-1 antibodies for use in any of the embodiments of the methods discussed above or herein. [0057] Other embodiments of the present disclosure will become apparent from a review of the ensuing detailed description. BRIEF DESCRIPTION OF THE FIGURES [0058] Figure 1 illustrates a proposed mechanism of action for the combination of the anti-MUC16 x CD28 antibody (REGN5668) and the anti-PD-1 antibody (cemiplimab). As discussed in Example 3, the effect of inducing signal 2 by REGN5668 while blocking an inhibitory signal with cemiplimab is being explored. As illustrated, the signaling activity in Module 1 is delivered through the cognate antigen receptors expressed by MHC-restricted tumor-specific T cells. [0059] Figure 2 illustrates a proposed mechanism of action for the combination of the anti-MUC16 x CD28 antibody (REGN5668) and the anti-MUC16 x CD3 antibody (REGN4018). As discussed in Example 3, the effect of inducing signal 2 by REGN5668 while directly engaging the TCR-CD3 complex with REGN4018 is being explored. As illustrated, the TCR-CD3 signaling activity is no longer dependent on T-cell recognition of a tumor-associated antigen. [0060] Figure 3 illustrates an embodiment of the patient-level study schema for Module 1, as discussed in Example 3, including administration of the anti-MUC16 x CD28 mAb1 (REGN5668) and the anti-PD-1 antibody (cemiplimab). [0061] Figure 4 illustrates an embodiment of the patient-level study schema for Module 2, as discussed in Example 3, including administration of the anti-MUC16 x CD28 mAb1 (REGN5668) and the anti-MUC16 x CD3 mAb2 (REGN4018). DETAILED DESCRIPTION [0062] Before the present disclosure is described, it is to be understood that this disclosure is not limited to particular methods and experimental conditions described, as such methods and conditions may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present disclosure will be limited only by the appended claims. Any embodiments or features of embodiments can be combined with one another, and such combinations are expressly encompassed within the scope of the present disclosure. Any specific value discussed above or herein may be combined with another related value discussed above or herein to recite a range with the values representing the upper and lower ends of the range, and such ranges are encompassed within the scope of the present disclosure. [0063] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. As used herein, the term "about," when used in reference to a particular recited numerical value, means that the value may vary from the recited value by no more than 1%. For example, as used herein, the expression "about 100" includes 99 and 101 and all values in between (e.g., 99.1, 99.2, 99.3, 99.4, etc.). [0064] Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, the preferred methods and materials are now described. All patents, applications and non-patent publications mentioned in this specification are incorporated herein by reference in their entireties. Methods for Treating or Inhibiting the Growth of Cancers [0065] The present disclosure includes methods for treating, ameliorating or reducing the severity of at least one symptom or indication, or inhibiting the growth of a MUC16-expressing cancer (e.g., recurrent ovarian cancer or endometrial cancer) in a subject. The methods according to this aspect of the disclosure comprise administering a therapeutically effective amount of a bispecific antibody or antigen-binding fragment thereof against MUC16 and CD28 in combination with (i) a therapeutically effective amount of an antibody or antigen-binding fragment thereof that specifically binds PD-1, or (ii) a therapeutically effective amount of a bispecific antibody or antigen-binding fragment thereof against MUC16 and CD3, to a subject in need thereof. As used herein, the terms "treat", "treating", or the like, mean to alleviate symptoms, eliminate the causation of symptoms either on a temporary or permanent basis, to delay or inhibit tumor growth, to reduce tumor cell load or tumor burden, to promote tumor regression, to cause tumor shrinkage, necrosis and/or disappearance, to prevent tumor recurrence, and/or to increase duration of survival of the subject. [0066] As used herein, the expression "a subject in need thereof" means a human or non-human mammal that exhibits one or more symptoms or indications of cancer, and/or who has been diagnosed with cancer, including a MUC16-expressing cancer (e.g., ovarian cancer, endometrial cancer, fallopian tube cancer or primary peritoneal cancer) and who needs treatment for the same. In many embodiments, the term "subject" may be interchangeably used with the term "patient". For example, a human subject may be diagnosed with a primary or a metastatic tumor and/or with one or more symptoms or indications including, but not limited to, enlarged lymph node(s), swollen abdomen, unexplained pain, unexplained weight loss, fever, night sweats, persistent fatigue, loss of appetite, and/or enlargement of spleen. The expression includes subjects with primary or established ovarian tumors or endometrial tumors. In specific embodiments, the expression includes human subjects that have and need treatment for ovarian cancer, endometrial cancer or another tumor expressing MUC16. In other specific embodiments, the expression includes subjects with MUC16+ tumors (e.g., a tumor with MUC16 expression as determined by flow cytometry). In certain embodiments, the expression "a subject in need thereof" includes patients with an ovarian cancer or endometrial cancer that is resistant to or refractory to or is inadequately controlled by prior therapy (e.g., treatment with a conventional anti-cancer agent, including platinum-based chemotherapy). For example, the expression includes subjects who have been treated with chemotherapy, such as a platinum-based chemotherapeutic agent (e.g., cisplatin) or a taxol compound (e.g., docetaxel). The expression also includes subjects with an ovarian tumor or endometrial tumor for which conventional anti-cancer therapy is inadvisable, for example, due to toxic side effects. For example, the expression includes patients who have received one or more cycles of chemotherapy or other anti-cancer therapy with toxic side effects. In certain embodiments, the expression "a subject in need thereof" includes patients with an ovarian tumor or endometrial tumor which has been treated but which has subsequently relapsed or metastasized. For example, patients with an ovarian tumor or endometrial tumor that may have received treatment with one or more anti-cancer agents leading to tumor regression; however, subsequently have relapsed with cancer resistant to the one or more anti-cancer agents (e.g., chemotherapy resistant cancer) are treated with the methods of the present disclosure. [0067] The expression "a subject in need thereof" also includes subjects who are at risk of developing ovarian cancer or endometrial cancer, e.g., persons with a family history of ovarian cancer or endometrial cancer, persons with a past history of infections associated with ovarian cancer, persons with mutations in the BRCA1/2 genes, or persons with an immune system compromised due to HIV infection or due to immunosuppressive medications. [0068] In certain embodiments, the methods of the present disclosure may be used to treat patients that show elevated levels of one or more cancer-associated biomarkers (e.g., programmed death ligand 1 (PD-L1), CA125, human epididymis protein 4 (HE4), and/or carcinoembryonic antigen (CEA)). For example, the methods of the present disclosure comprise administering a therapeutically effective amount of a bispecific anti-MUC16/anti-CD28 antibody in combination with an anti-PD-1 antibody or a bispecific anti-MUC16/anti-CD3 antibody to a patient with an elevated level of PD-L1 and/or CA125. [0069] In certain embodiments, the methods of the present disclosure are used in a subject with an ovarian cancer, an endometrial cancer, or another MUC16-expressing cancer. The terms "tumor", "cancer" and "malignancy" are interchangeably used herein. The term "ovarian cancer", as used herein, refers to tumors of the ovary and fallopian tube, and includes serous cancer, endometrioid carcinoma, clear cell carcinoma, and mucinous carcinoma. The term “ovarian cancer” is not intended to encompass carcinosarcoma. The term “endometrial cancer” refers to tumors of cells in the uterus or endometrium. [0070] According to certain embodiments, the present disclosure includes methods for treating, or delaying or inhibiting the growth of a tumor. In certain embodiments, the present disclosure includes methods to promote tumor regression. In certain embodiments, the present disclosure includes methods to reduce tumor cell load or to reduce tumor burden. In certain embodiments, the present disclosure includes methods to prevent tumor recurrence. The methods, according to this aspect of the disclosure, comprise administering a therapeutically effective amount of a bispecific anti- MUC16/anti-CD28 antibody in combination with an anti-PD-1 antibody or a bispecific anti- MUC16/anti-CD3 antibody to a subject in need thereof, wherein each antibody is administered to the subject in multiple doses, e.g., as part of a specific therapeutic dosing regimen. For example, the therapeutic dosing regimen may comprise administering one or more doses of an anti-MUC16 x CD28 antibody to the subject at a frequency of about once a day, once every two days, once every three days, once every four days, once every five days, once every six days, once a week, once every two weeks, once every three weeks, once every four weeks, once a month, once every two months, once every three months, once every four months, or less frequently. In certain embodiments, the anti-MUC16 x anti-CD28 antibody is administered once a week. In certain embodiments, the one or more doses of anti-PD-1 antibody are administered in combination with the one or more doses of a therapeutically effective amount of a bispecific anti-MUC16/anti-CD28 antibody, wherein the one or more doses of the anti-PD-1 antibody are administered to the subject at a frequency of about once a day, once every two days, once every three days, once every four days, once every five days, once every six days, once a week, once every two weeks, once every three weeks, once every four weeks, once a month, once every two months, once every three months, once every four months, or less frequently. In certain embodiments, the anti-PD-1 antibody is administered to the subject once every three weeks. In certain embodiments, the one or more doses of bispecific anti-MUC16/anti-CD3 antibody are administered in combination with the one or more doses of a therapeutically effective amount of a bispecific anti-MUC16/anti-CD28 antibody, wherein the one or more doses of the bispecific anti-MUC16/anti-CD3 antibody are administered to the subject at a frequency of about once a day, once every two days, once every three days, once every four days, once every five days, once every six days, once a week, once every two weeks, once every three weeks, once every four weeks, once a month, once every two months, once every three months, once every four months, or less frequently. In certain embodiments, the bispecific anti-MUC16/anti-CD3 antibody is administered to the subject once a week. [0071] In certain embodiments, each dose of the anti-MUC16/anti-CD28 antibody is administered in two or more fractions, e.g., in 2-5 fractions ("split dosing") within the given dosing period. The anti-MUC16/anti-CD28 bispecific antibody may be administered in split doses to reduce or eliminate the cytokine "spikes" induced in response to administration of the antibody. Cytokine spikes refer to the clinical symptoms of the cytokine release syndrome ("cytokine storm") and infusion related reactions. In certain embodiments, the methods of the present disclosure comprise administering one or more doses of anti-PD-1 antibody in combination with the one or more doses of a bispecific anti-MUC16/anti-CD28 antibody to a subject in need thereof, wherein a dose of the anti- MUC16/CD28 bispecific antibody is administered as split doses, or in more than 1 fractions, e.g., as 2 fractions, as 3 fractions, as 4 fractions or as 5 fractions within the given dosing period. In certain embodiments, a dose of the anti-MUC16/CD28 bispecific antibody is split into 2 or more fractions, wherein each fraction comprises an amount of the antibody equal to the other fractions. In certain embodiments, a dose of the anti-MUC16/CD28 bispecific antibody is administered split into 2 or more fractions, wherein the fractions comprise unequal amounts of the antibody, e.g., more than or less than the first fraction. In certain embodiments, the methods of the present disclosure comprise administering one or more doses of a bispecific anti-MUC16/anti-CD3 antibody in combination with the one or more doses of a bispecific anti-MUC16/anti-CD28 antibody to a subject in need thereof, wherein a dose of the anti-MUC16/anti-CD3 bispecific antibody and/or a dose of the anti- MUC16/CD28 bispecific antibody is administered as split doses, or in more than 1 fractions, e.g., as 2 fractions, as 3 fractions, as 4 fractions or as 5 fractions within the given dosing period. In certain embodiments, a dose of the anti-MUC16/anti-CD3 bispecific antibody and/or a dose of the anti- MUC16/CD28 bispecific antibody is split into 2 or more fractions, wherein each fraction comprises an amount of the antibody equal to the other fractions. In certain embodiments, a dose of the anti- MUC16/anti-CD3 bispecific antibody and/or a dose of the anti-MUC16/CD28 bispecific antibody is administered split into 2 or more fractions, wherein the fractions comprise unequal amounts of the antibody, e.g., more than or less than the first fraction. [0072] In certain embodiments, the present disclosure includes methods to inhibit, retard or stop tumor metastasis or tumor infiltration into peripheral organs. The methods, according to this aspect, comprise administering a therapeutically effective amount of a bispecific anti-MUC16/anti-CD28 antibody in combination with an anti-PD-1 antibody or a bispecific anti-MUC16/anti-CD3 antibody to a subject in need thereof. [0073] In specific embodiments, the present disclosure provides methods for increased anti- tumor efficacy or increased tumor inhibition. Certain embodiments, according to this aspect of the disclosure, comprise administering to a subject with a MUC16-expressing cancer (e.g., ovarian cancer or endometrial cancer) a therapeutically effective amount of a bispecific anti-MUC16/anti- CD28 antibody prior to administering a therapeutically effective amount of an anti-PD-1 antibody, wherein the bispecific anti-MUC16/anti-CD28 antibody may be administered about 1 day, more than 1 day, more than 2 days, more than 3 days, more than 4 days, more than 5 days, more than 6 days, more than 7 days, or more than 8 days prior to the anti-PD-1 antibody. In some cases, the bispecific anti-MUC16/anti-CD28 antibody is administered for a period of about 1 week, about 2 weeks, or about 3 weeks prior to administration of the anti-PD-1 antibody. Certain embodiments, according to this aspect of the disclosure, comprise administering to a subject with a MUC16- expressing cancer (e.g., ovarian cancer or endometrial cancer) a therapeutically effective amount of a bispecific anti-MUC16/anti-CD3 antibody prior to administering a therapeutically effective amount of a bispecific anti-MUC16/anti-CD28 antibody, wherein the bispecific anti-MUC16/anti-CD3 antibody may be administered about 1 day, more than 1 day, more than 2 days, more than 3 days, more than 4 days, more than 5 days, more than 6 days, more than 7 days, or more than 8 days prior to the bispecific anti-MUC16/anti-CD28 antibody. In some cases, the bispecific anti- MUC16/anti-CD23 antibody is administered for a period of about 1 week, about 2 weeks, about 3 weeks, about 4 weeks, or about 5 weeks prior to administration of the bispecific anti-MUC16/anti- CD28 antibody. In certain embodiments, the methods provide for increased tumor inhibition, e.g., by about 20%, more than 20%, more than 30%, more than 40% more than 50%, more than 60%, more than 70% or more than 80% as compared to a subject administered any one of the antibodies alone. [0074] In certain embodiments, the methods of the present disclosure are used to treat a patient with a MRD-positive disease. Minimum residual disease (MRD) refers to small numbers of cancer cells that remain in the patient during or after treatment, wherein the patient may or may not show symptoms or signs of the disease. Such residual cancer cells, if not eliminated, frequently lead to relapse of the disease. The present disclosure includes methods to inhibit and/or eliminate residual cancer cells in a patient upon MRD testing. MRD may be assayed according to methods known in the art (e.g., MRD flow cytometry). The methods, according to this aspect of the disclosure, comprise administering a bispecific anti-MUC16/anti-CD28 antibody in combination with an anti-PD- 1 antibody or a bispecific anti-MUC16/anti-CD3 antibody to a subject in need thereof. [0075] The methods of the present disclosure, according to certain embodiments, comprise administering to a subject a therapeutically effective amount of a bispecific anti-MUC16/anti-CD28 antibody in combination with an anti-PD-1 antibody or a bispecific anti-MUC16/anti-CD3 antibody and, optionally, a third therapeutic agent. The third therapeutic agent may be an agent selected from the group consisting of, e.g., radiation, chemotherapy, surgery, a cancer vaccine, a PD-L1 inhibitor (e.g., an anti-PD-L1 antibody), a LAG3 inhibitor (e.g., an anti-LAG3 antibody), a CTLA-4 inhibitor (e.g., an anti-CTLA-4 antibody), a TIM3 inhibitor, a BTLA inhibitor, a TIGIT inhibitor, a CD47 inhibitor, an indoleamine-2,3-dioxygenase (IDO) inhibitor, a vascular endothelial growth factor (VEGF) antagonist, an Ang2 inhibitor, a transforming growth factor beta (TGF.beta.) inhibitor, an epidermal growth factor receptor (EGFR) inhibitor, an antibody to a tumor-specific antigen (e.g., CA9, CA125, melanoma-associated antigen 3 (MAGE3), carcinoembryonic antigen (CEA), vimentin, tumor-M2-PK, prostate-specific antigen (PSA), mucin-1, MART-1, and CA19-9), a vaccine (e.g., Bacillus Calmette-Guerin), granulocyte-macrophage colony-stimulating factor, an oncolytic virus, a cytotoxin, a chemotherapeutic agent, an IL-6R inhibitor, an IL-4R inhibitor, an IL-10 inhibitor, a cytokine such as IL-2, IL-7, IL-21, and IL-15, an anti-inflammatory drug such as corticosteroids, and non-steroidal anti-inflammatory drugs, and a dietary supplement such as anti- oxidants. In certain embodiments, the antibodies may be administered in combination with therapy including a chemotherapeutic agent (e.g., paclitaxel, carboplatin, doxorubicin, cyclophosphamide, cisplatin, gemcitabine or docetaxel), radiation and surgery. As used herein, the phrase “in combination with" means that the antibodies are administered to the subject at the same time as, just before, or just after administration of the third therapeutic agent. In certain embodiments, the third therapeutic agent is administered as a co-formulation with the antibodies, or with one of the antibodies In certain embodiments, the third therapeutic agent is separately administered. [0076] In certain embodiments, the methods of the present disclosure comprise administering to a subject in need thereof a therapeutically effective amount of a bispecific anti-MUC16/anti-CD28 antibody in combination with an anti-PD-1 antibody or a bispecific anti-MUC16/anti-CD3 antibody. Where either combination is administered, the administration of the antibodies leads to increased inhibition of tumor growth. In certain embodiments, tumor growth is inhibited by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70% or about 80% as compared to an untreated subject or a subject administered with either antibody as monotherapy, respectively. In certain embodiments, the administration of either combination leads to increased tumor regression, tumor shrinkage and/or disappearance. In certain embodiments, the administration of either combination leads to delay in tumor growth and development, e.g., tumor growth may be delayed by about 3 days, more than 3 days, about 7 days, more than 7 days, more than 15 days, more than 1 month, more than 3 months, more than 6 months, more than 1 year, more than 2 years, or more than 3 years as compared to an untreated subject or a subject treated with either antibody as monotherapy, respectively. In certain embodiments, administration of either combination prevents tumor recurrence and/or increases duration of survival of the subject, e.g., increases duration of survival by more than 15 days, more than 1 month, more than 3 months, more than 6 months, more than 12 months, more than 18 months, more than 24 months, more than 36 months, or more than 48 months relative to an untreated subject or a subject which is administered either antibody as monotherapy, respectively. In certain embodiments, administration of either combination increases progression-free survival or overall survival. In certain embodiments, administration of either combination increases response and duration of response in a subject, e.g., by more than 2%, more than 3%, more than 4%, more than 5%, more than 6%, more than 7%, more than 8%, more than 9%, more than 10%, more than 20%, more than 30%, more than 40% or more than 50% over an untreated subject or a subject which has received either antibody as monotherapy, respectively. In certain embodiments, administration of either combination to a subject with a MUC16-expressing cancer (e.g., ovarian cancer or endometrial cancer) leads to complete disappearance of all evidence of tumor cells ("complete response"). In certain embodiments, administration of either combination to a subject with a MUC16-expressing cancer (e.g., ovarian cancer or endometrial cancer) leads to at least 30% or more decrease in tumor cells or tumor size ("partial response"). In certain embodiments, administration of either combination to a subject with a MUC16-expressing cancer (e.g., ovarian cancer or endometrial cancer) leads to complete or partial disappearance of tumor cells/lesions including new measurable lesions. Tumor reduction can be measured by any of the methods known in the art, e.g., X-rays, positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI), cytology, histology, or molecular genetic analyses. In certain embodiments, administration of either combination produces a synergistic anti-tumor effect that exceeds the combined effects of the two agents when administered alone. [0077] In certain cases, the response of a subject to therapy is categorized as a complete response (CR), a partial response (PR), progressive disease (PD), or as stable disease (SD). A CR is defined as disappearance of all target lesions, and a reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm (<1 cm). A PR is defined as an at least 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. PD is defined as an at least 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (0.5 cm). (Note: the appearance of one or more new lesions is also considered a progression). SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Anti-PD-1 Antibodies and Antigen-Binding Fragments Thereof [0078] According to certain exemplary embodiments of the present disclosure, the methods comprise administering a therapeutically effective amount of an anti-PD-1 antibody or antigen- binding fragment thereof. The term “anti-PD-1 antibody or antigen-binding fragment thereof” refers to and is used interchangeably with the term “antibody or antigen-binding fragment thereof that specifically binds to PD-1.” The term "antibody," as used herein, includes immunoglobulin molecules comprising four polypeptide chains, two heavy (H) chains and two light (L) chains inter- connected by disulfide bonds, as well as multimers thereof (e.g., IgM). In a typical antibody, each heavy chain comprises a heavy chain variable region (abbreviated herein as HCVR or V_H) and a heavy chain constant region. The heavy chain constant region comprises three domains, C_H1, C_H2 and C_H3. Each light chain comprises a light chain variable region (abbreviated herein as LCVR or V_L) and a light chain constant region. The light chain constant region comprises one domain (C_L1). The V_H and V_L regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDRs), interspersed with regions that are more conserved, termed framework regions (FR). Each V_H and V_L is composed of three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. In different embodiments of the disclosure, the FRs of the anti-IL-4R antibody (or antigen-binding portion thereof) may be identical to the human germline sequences, or may be naturally or artificially modified. An amino acid consensus sequence may be defined based on a side-by-side analysis of two or more CDRs. [0079] The term "antibody," as used herein, also includes antigen-binding fragments of full antibody molecules. The terms "antigen-binding portion" of an antibody, "antigen-binding fragment" of an antibody, and the like, as used herein, include any naturally occurring, enzymatically obtainable, synthetic, or genetically engineered polypeptide or glycoprotein that specifically binds an antigen to form a complex. Antigen-binding fragments of an antibody may be derived, e.g., from full antibody molecules using any suitable standard techniques such as proteolytic digestion or recombinant genetic engineering techniques involving the manipulation and expression of DNA encoding antibody variable and optionally constant domains. Such DNA is known and/or is readily available from, e.g., commercial sources, DNA libraries (including, e.g., phage-antibody libraries), or can be synthesized. The DNA may be sequenced and manipulated chemically or by using molecular biology techniques, for example, to arrange one or more variable and/or constant domains into a suitable configuration, or to introduce codons, create cysteine residues, modify, add or delete amino acids, etc. [0080] Non-limiting examples of antigen-binding fragments include: (i) Fab fragments; (ii) F(ab')2 fragments; (iii) Fd fragments; (iv) Fv fragments; (v) single-chain Fv (scFv) molecules; (vi) dAb fragments; and (vii) minimal recognition units consisting of the amino acid residues that mimic the hypervariable region of an antibody (e.g., an isolated complementarity determining region (CDR) such as a CDR3 peptide), or a constrained FR3-CDR3-FR4 peptide. Other engineered molecules, such as domain-specific antibodies, single domain antibodies, domain-deleted antibodies, chimeric antibodies, CDR-grafted antibodies, diabodies, triabodies, tetrabodies, minibodies, nanobodies (e.g. monovalent nanobodies, bivalent nanobodies, etc.), small modular immunopharmaceuticals (SMIPs), and shark variable IgNAR domains, are also encompassed within the expression "antigen- binding fragment," as used herein. [0081] An antigen-binding fragment of an antibody will typically comprise at least one variable domain. The variable domain may be of any size or amino acid composition and will generally comprise at least one CDR which is adjacent to or in frame with one or more framework sequences. In antigen-binding fragments having a V_H domain associated with a V_L domain, the V_H and V_L domains may be situated relative to one another in any suitable arrangement. For example, the variable region may be dimeric and contain V_H-V_H, V_H-V_L or V_L-V_L dimers. Alternatively, the antigen- binding fragment of an antibody may contain a monomeric V_H or V_L domain. [0082] In certain embodiments, an antigen-binding fragment of an antibody may contain at least one variable domain covalently linked to at least one constant domain. Non-limiting, exemplary configurations of variable and constant domains that may be found within an antigen-binding fragment of an antibody of the present disclosure include: (i) V_H-C_H1; (ii) V_H-C_H2; (iii) V_H-C_H3; (iv) V_H-C_H1-C_H2; (v) V_H-C_H1-C_H2-C_H3; (vi) V_H-C_H2-C_H3; (vii) V_H-C_L; (viii) V_L-C_H1; (ix) V_L-C_H2; (x) V_L-C_H3; (xi) V_L-C_H1-C_H2; (xii) V_L-C_H1-C_H2-C_H3; (xiii) V_L-C_H2-C_H3; and (xiv) V_L-C_L. In any configuration of variable and constant domains, including any of the exemplary configurations listed above, the variable and constant domains may be either directly linked to one another or may be linked by a full or partial hinge or linker region. A hinge region may consist of at least 2 (e.g., 5, 10, 15, 20, 40, 60 or more) amino acids which result in a flexible or semi-flexible linkage between adjacent variable and/or constant domains in a single polypeptide molecule. Moreover, an antigen-binding fragment of an antibody of the present disclosure may comprise a homo-dimer or hetero-dimer (or other multimer) of any of the variable and constant domain configurations listed above in non-covalent association with one another and/or with one or more monomeric VH or VL domain (e.g., by disulfide bond(s)). [0083] The term "antibody," as used herein, also includes multispecific (e.g., bispecific) antibodies. A multispecific antibody or antigen-binding fragment of an antibody will typically comprise at least two different variable domains, wherein each variable domain is capable of specifically binding to a separate antigen or to a different epitope on the same antigen. Any multispecific antibody format may be adapted for use in the context of an antibody or antigen- binding fragment of an antibody of the present disclosure using routine techniques available in the art. For example, the present disclosure includes methods comprising the use of bispecific antibodies wherein one arm of an immunoglobulin is specific for PD-1 or a fragment thereof, and the other arm of the immunoglobulin is specific for a second therapeutic target or is conjugated to a therapeutic moiety. Exemplary bispecific formats that can be used in the context of the present disclosure include, without limitation, e.g., scFv-based or diabody bispecific formats, IgG-scFv fusions, dual variable domain (DVD)-Ig, Quadroma, knobs-into-holes, common light chain (e.g., common light chain with knobs-into-holes, etc.), CrossMab, CrossFab, (SEED) body, leucine zipper, Duobody, IgG1/IgG2, dual acting Fab (DAF)-IgG, and Mab.sup.2 bispecific formats (see, e.g., Klein et al.2012, mAbs 4:6, 1-11, and references cited therein, for a review of the foregoing formats). Bispecific antibodies can also be constructed using peptide/nucleic acid conjugation, e.g., wherein unnatural amino acids with orthogonal chemical reactivity are used to generate site-specific antibody-oligonucleotide conjugates which then self-assemble into multimeric complexes with defined composition, valency and geometry. (See, e.g., Kazane et al., J. Am. Chem. Soc. [Epub: Dec.4, 2012]). [0084] The antibodies used in the methods of the present disclosure may be human antibodies. The term "human antibody," as used herein, is intended to include antibodies having variable and constant regions derived from human germline immunoglobulin sequences. The human antibodies of the disclosure may nonetheless include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo), for example in the CDRs and in particular CDR3. However, the term "human antibody," as used herein, is not intended to include antibodies in which CDR sequences derived from the germline of another mammalian species, such as a mouse, have been grafted onto human framework sequences. [0085] The antibodies used in the methods of the present disclosure may be recombinant human antibodies. The term "recombinant human antibody," as used herein, is intended to include all human antibodies that are prepared, expressed, created or isolated by recombinant means, such as antibodies expressed using a recombinant expression vector transfected into a host cell (described further below), antibodies isolated from a recombinant, combinatorial human antibody library (described further below), antibodies isolated from an animal (e.g., a mouse) that is transgenic for human immunoglobulin genes (see e.g., Taylor et al. (1992) Nucl. Acids Res. 20:6287-6295) or antibodies prepared, expressed, created or isolated by any other means that involves splicing of human immunoglobulin gene sequences to other DNA sequences. Such recombinant human antibodies have variable and constant regions derived from human germline immunoglobulin sequences. In certain embodiments, however, such recombinant human antibodies are subjected to in vitro mutagenesis (or, when an animal transgenic for human Ig sequences is used, in vivo somatic mutagenesis) and thus the amino acid sequences of the VH and VL regions of the recombinant antibodies are sequences that, while derived from and related to human germline VH and VL sequences, may not naturally exist within the human antibody germline repertoire in vivo. [0086] According to certain embodiments, the antibodies used in the methods of the present disclosure specifically bind PD-1. The term "specifically binds," or the like, means that an antibody or antigen-binding fragment thereof forms a complex with an antigen that is relatively stable under physiologic conditions. Methods for determining whether an antibody specifically binds to an antigen are well known in the art and include, for example, equilibrium dialysis, surface plasmon resonance, and the like. For example, an antibody that "specifically binds" PD-1, as used in the context of the present disclosure, includes antibodies that bind PD-1 or portion thereof with a K_D of less than about 500 nM, less than about 300 nM, less than about 200 nM, less than about 100 nM, less than about 90 nM, less than about 80 nM, less than about 70 nM, less than about 60 nM, less than about 50 nM, less than about 40 nM, less than about 30 nM, less than about 20 nM, less than about 10 nM, less than about 5 nM, less than about 4 nM, less than about 3 nM, less than about 2 nM, less than about 1 nM or less than about 0.5 nM, as measured in a surface plasmon resonance assay. An isolated antibody that specifically binds human PD-1 may, however, have cross-reactivity to other antigens, such as PD-1 molecules from other (non-human) species. [0087] According to certain exemplary embodiments of the present disclosure, the anti-PD-1 antibody, or antigen-binding fragment thereof comprises a heavy chain variable region (HCVR), light chain variable region (LCVR), and/or complementarity determining regions (CDRs) comprising any of the amino acid sequences of the anti-PD-1 antibodies as set forth in US Patent Publication No.20150203579. In certain exemplary embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof that can be used in the context of the methods of the present disclosure comprises the heavy chain complementarity determining regions (HCDRs) of a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 51 and the light chain complementarity determining regions (LCDRs) of a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 55. According to certain embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises three HCDRs (HCDR1, HCDR2 and HCDR3) and three LCDRs (LCDR1, LCDR2 and LCDR3), wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 52; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 53; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 54; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 56; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 57; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 58. In yet other embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises an HCVR comprising SEQ ID NO: 51 and an LCVR comprising SEQ ID NO: 55. In certain embodiments, the methods of the present disclosure comprise the use of an anti-PD-1 antibody, wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 59. In some embodiments, the anti-PD-1 antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 60. An exemplary antibody comprising a HCVR comprising the amino acid sequence of SEQ ID NO: 51 and a LCVR comprising the amino acid sequence of SEQ ID NO: 55 is the fully human anti-PD-1 antibody known as REGN2810 (also known as cemiplimab; LIBTAYO®). According to certain exemplary embodiments, the methods of the present disclosure comprise the use of REGN2810, or a bioequivalent thereof. The term "bioequivalent", as used herein, refers to anti-PD-1 antibodies or PD-1-binding proteins or fragments thereof that are pharmaceutical equivalents or pharmaceutical alternatives whose rate and/or extent of absorption do not show a significant difference with that of REGN2810 when administered at the same molar dose under similar experimental conditions, either single dose or multiple dose. In the context of the disclosure, the term refers to antigen-binding proteins that bind to PD-1 which do not have clinically meaningful differences with REGN2810 in their safety, purity and/or potency. [0088] Other anti-PD-1 antibodies that can be used in the context of the methods of the present disclosure include, e.g., the antibodies referred to and known in the art as nivolumab (U.S. Pat. No. 8,008,449), pembrolizumab (U.S. Pat. No.8,354,509), MEDI0608 (U.S. Pat. No.8,609,089), pidilizumab (U.S. Pat. No.8,686,119), or any of the anti-PD-1 antibodies as set forth in U.S. Pat. Nos.6,808,710, 7,488,802, 8,168,757, 8,354,509, 8,779,105, or 8,900,587. [0089] The anti-PD-1 antibodies used in the context of the methods of the present disclosure may have pH-dependent binding characteristics. For example, an anti-PD-1 antibody for use in the methods of the present disclosure may exhibit reduced binding to PD-1 at acidic pH as compared to neutral pH. Alternatively, an anti-PD-1 antibody of the disclosure may exhibit enhanced binding to its antigen at acidic pH as compared to neutral pH. The expression "acidic pH" includes pH values less than about 6.2, e.g., about 6.0, 5.95, 5.9, 5.85, 5.8, 5.75, 5.7, 5.65, 5.6, 5.55, 5.5, 5.45, 5.4, 5.35, 5.3, 5.25, 5.2, 5.15, 5.1, 5.05, 5.0, or less. As used herein, the expression "neutral pH" means a pH of about 7.0 to about 7.4. The expression "neutral pH" includes pH values of about 7.0, 7.05, 7.1, 7.15, 7.2, 7.25, 7.3, 7.35, and 7.4. [0090] In certain instances, "reduced binding to PD-1 at acidic pH as compared to neutral pH" is expressed in terms of a ratio of the KD value of the antibody binding to PD-1 at acidic pH to the KD value of the antibody binding to PD-1 at neutral pH (or vice versa). For example, an antibody or antigen-binding fragment thereof may be regarded as exhibiting "reduced binding to PD-1 at acidic pH as compared to neutral pH" for purposes of the present disclosure if the antibody or antigen- binding fragment thereof exhibits an acidic/neutral KD ratio of about 3.0 or greater. In certain exemplary embodiments, the acidic/neutral KD ratio for an antibody or antigen-binding fragment of the present disclosure can be about 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10.0, 10.5, 11.0, 11.5, 12.0, 12.5, 13.0, 13.5, 14.0, 14.5, 15.0, 20.0, 25.0, 30.0, 40.0, 50.0, 60.0, 70.0, 100.0, or greater. [0091] Antibodies with pH-dependent binding characteristics may be obtained, e.g., by screening a population of antibodies for reduced (or enhanced) binding to a particular antigen at acidic pH as compared to neutral pH. Additionally, modifications of the antigen-binding domain at the amino acid level may yield antibodies with pH-dependent characteristics. For example, by substituting one or more amino acids of an antigen-binding domain (e.g., within a CDR) with a histidine residue, an antibody with reduced antigen-binding at acidic pH relative to neutral pH may be obtained. As used herein, the expression "acidic pH" means a pH of 6.0 or less. Bispecific Anti-MUC16 x Anti-CD28 Antibodies [0092] According to certain exemplary embodiments of the present disclosure, the methods comprise administering a therapeutically effective amount of a bispecific antibody comprising a first antigen-binding domain that specifically binds MUC16 and a second antigen-binding domain that binds CD28. Such antibodies may be referred to herein as, e.g., "anti-MUC16/anti-CD28," or "anti- MUC16 x anti-CD28" or "MUC16 x CD28" bispecific antibodies, or other similar terminology. [0093] As used herein, the expression "bispecific antibody" refers to an immunoglobulin protein comprising at least a first antigen-binding domain and a second antigen-binding domain. In the context of the present disclosure, the first antigen-binding domain specifically binds a first antigen (e.g., MUC16), and the second antigen-binding domain specifically binds a second, distinct antigen (e.g., CD28). Each antigen-binding domain of a bispecific antibody comprises a heavy chain variable domain (HCVR) and a light chain variable domain (LCVR), each comprising three CDRs. In the context of a bispecific antibody, the CDRs of the first antigen-binding domain may be designated with the prefix "A" and the CDRs of the second antigen-binding domain may be designated with the prefix "B". Thus, the CDRs of the first antigen-binding domain may be referred to herein as A-HCDR1, A-HCDR2, and A-HCDR3; and the CDRs of the second antigen-binding domain may be referred to herein as B-HCDR1, B-HCDR2, and B-HCDR3. [0094] The first antigen-binding domain and the second antigen-binding domain are each connected to a separate multimerizing domain. As used herein, a "multimerizing domain" is any macromolecule, protein, polypeptide, peptide, or amino acid that has the ability to associate with a second multimerizing domain of the same or similar structure or constitution. In the context of the present disclosure, the multimerizing component is an Fc portion of an immunoglobulin (comprising a CH2-CH3 domain), e.g., an Fc domain of an IgG selected from the isotypes IgG1, IgG2, IgG3, and IgG4, as well as any allotype within each isotype group. [0095] Bispecific antibodies of the present disclosure typically comprise two multimerizing domains, e.g., two Fc domains that are each individually part of a separate antibody heavy chain. The first and second multimerizing domains may be of the same IgG isotype such as, e.g., IgG1/IgG1, IgG2/IgG2, IgG4/IgG4. Alternatively, the first and second multimerizing domains may be of different IgG isotypes such as, e.g., IgG1/IgG2, IgG1/IgG4, IgG2/IgG4, etc. [0096] Any bispecific antibody format or technology may be used to make the bispecific antibodies of the present disclosure. For example, an antibody or fragment thereof having a first antigen binding specificity can be functionally linked (e.g., by chemical coupling, genetic fusion, noncovalent association or otherwise) to one or more other molecular entities, such as another antibody or antibody fragment having a second antigen-binding specificity to produce a bispecific antibody. Specific exemplary bispecific formats that can be used in the context of the present disclosure include, without limitation, e.g., scFv-based or diabody bispecific formats, IgG-scFv fusions, dual variable domain (DVD)-Ig, Quadroma, knobs-into-holes, common light chain (e.g., common light chain with knobs-into-holes, etc.), CrossMab, CrossFab, (SEED)body, leucine zipper, Duobody, IgG1/IgG2, dual acting Fab (DAF)-IgG, and Mab₂ bispecific formats (see, e.g., Klein et al. 2012, mAbs 4:6, 1-11, and references cited therein, for a review of the foregoing formats). [0097] In the context of bispecific antibodies of the present disclosure, Fc domains may comprise one or more amino acid changes (e.g., insertions, deletions or substitutions) as compared to the wild-type, naturally occurring version of the Fc domain. For example, the disclosure includes bispecific antibodies comprising one or more modifications in the Fc domain that results in a modified Fc domain having a modified binding interaction (e.g., enhanced or diminished) between Fc and FcRn. In one embodiment, the bispecific antibody comprises a modification in a C_H2 or a C_H3 region, wherein the modification increases the affinity of the Fc domain to FcRn in an acidic environment (e.g., in an endosome where pH ranges from about 5.5 to about 6.0). Non-limiting examples of such Fc modifications are disclosed in US Patent Publication No.20150266966, incorporated herein in its entirety. [0098] The present disclosure also includes bispecific antibodies comprising a first CH3 domain and a second Ig CH3 domain, wherein the first and second Ig CH3 domains differ from one another by at least one amino acid, and wherein at least one amino acid difference reduces binding of the bispecific antibody to Protein A as compared to a bi-specific antibody lacking the amino acid difference. In one embodiment, the first Ig CH3 domain binds Protein A and the second Ig CH3 domain contains a mutation that reduces or abolishes Protein A binding such as an H95R modification (by IMGT exon numbering; H435R by EU numbering). The second CH3 may further comprise a Y96F modification (by IMGT; Y436F by EU). See, for example, US Patent No. 8,586,713. Further modifications that may be found within the second CH3 include: D16E, L18M, N44S, K52N, V57M, and V82I (by IMGT; D356E, L358M, N384S, K392N, V397M, and V422I by EU) in the case of IgG1 antibodies; N44S, K52N, and V82I (IMGT; N384S, K392N, and V422I by EU) in the case of IgG2 antibodies; and Q15R, N44S, K52N, V57M, R69K, E79Q, and V82I (by IMGT; Q355R, N384S, K392N, V397M, R409K, E419Q, and V422I by EU) in the case of IgG4 antibodies. [0099] In certain embodiments, the Fc domain may be chimeric, combining Fc sequences derived from more than one immunoglobulin isotype. For example, a chimeric Fc domain can comprise part or all of a C_H2 sequence derived from a human IgG1, human IgG2 or human IgG4 C_H2 region, and part or all of a C_H3 sequence derived from a human IgG1, human IgG2 or human IgG4. A chimeric Fc domain can also contain a chimeric hinge region. For example, a chimeric hinge may comprise an "upper hinge" sequence, derived from a human IgG1, a human IgG2 or a human IgG4 hinge region, combined with a "lower hinge" sequence, derived from a human IgG1, a human IgG2 or a human IgG4 hinge region. A particular example of a chimeric Fc domain that can be included in any of the antibodies set forth herein comprises, from N- to C-terminus: [IgG4 C_H1]-[IgG4 upper hinge]- [IgG2 lower hinge]-[IgG4 CH2]-[IgG4 CH3]. Another example of a chimeric Fc domain that can be included in any of the antibodies set forth herein comprises, from N- to C-terminus: [IgG1 C_H1]- [IgG1 upper hinge]-[IgG2 lower hinge]-[IgG4 CH2]-[IgG1 CH3]. These and other examples of chimeric Fc domains or chimeric heavy chain constant regions that can be included in any of the antibodies of the present disclosure are described in US Patent Publication No.20140243504, which is herein incorporated in its entirety. Chimeric Fc domains and chimeric heavy chain constant regions having these general structural arrangements, and variants thereof, can have altered Fc receptor binding, which in turn affects Fc effector function. [0100] According to certain exemplary embodiments of the present disclosure, the bispecific anti- MUC16/anti-CD28 antibody, or antigen-binding fragment thereof comprises heavy chain variable regions (A-HCVR and B-HCVR), light chain variable regions (A-LCVR and B-LCVR), and/or complementarity determining regions (CDRs) comprising any of the amino acid sequences of the bispecific anti-MUC16/anti-CD28 antibodies as set forth in WO 2020/132024. In certain exemplary embodiments, the bispecific anti- MUC16/anti-CD28 antibody or antigen-binding fragment thereof that can be used in the context of the methods of the present disclosure comprises: (a) a first antigen-binding arm that binds MUC16 comprising the heavy chain complementarity determining regions (A-HCDR1, A-HCDR2 and A-HCDR3) of a heavy chain variable region (A-HCVR) comprising the amino acid sequence of SEQ ID NO: 1 and the light chain complementarity determining regions (A-LCDR1, A-LCDR2 and A-LCDR3) of a light chain variable region (A-LCVR) comprising the amino acid sequence of SEQ ID NO: 9; and (b) a second antigen-binding arm that binds CD28 comprising the heavy chain CDRs (B-HCDR1, B-HCDR2 and B-HCDR3) of a HCVR (B-HCVR) comprising an amino acid sequence of SEQ ID NO: 5, and the light chain CDRs (B-LCDR1, B-LCDR2 and B-LCDR3) of a LCVR (B-LCVR) comprising the amino acid sequence of SEQ ID NO: 9. According to certain embodiments, the A-HCDR1 comprises the amino acid sequence of SEQ ID NO: 2; the A-HCDR2 comprises the amino acid sequence of SEQ ID NO: 3; the A-HCDR3 comprises the amino acid sequence of SEQ ID NO: 4; the A-LCDR1 comprises the amino acid sequence of SEQ ID NO: 10; the A-LCDR2 comprises the amino acid sequence of SEQ ID NO: 11; the A-LCDR3 comprises the amino acid sequence of SEQ ID NO: 12; the B-HCDR1 comprises the amino acid sequence of SEQ ID NO: 6; the B-HCDR2 comprises the amino acid sequence of SEQ ID NO: 7; and the B-HCDR3 comprises the amino acid sequence of SEQ ID NO: 8; and the B-LCDR1 comprises the amino acid sequence of SEQ ID NO: 10; the B-LCDR2 comprises the amino acid sequence of SEQ ID NO: 11; the B-LCDR3 comprises the amino acid sequence of SEQ ID NO: 12. In yet other embodiments, the bispecific anti-MUC16/anti-CD28 antibody or antigen-binding fragment thereof comprises: (a) a first antigen-binding arm that binds MUC16 comprising a HCVR (A-HCVR) comprising SEQ ID NO: 1 and a LCVR (A-LCVR) comprising SEQ ID NO: 9; and (b) a second antigen-binding arm that binds CD28 comprising a HCVR (B-HCVR) comprising SEQ ID NO: 5, and a LCVR (B-LCVR) comprising SEQ ID NO: 9. In certain exemplary embodiments, the bispecific anti-MUC16 x CD28 antibody comprises a MUC16- binding arm comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 13 and a light chain comprising the amino acid sequence of SEQ ID NO: 15, and a CD28-binding arm comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 14 and a light chain comprising the amino acid sequence of SEQ ID NO: 15. [0101] In certain exemplary embodiments, the bispecific anti- MUC16/anti-CD28 antibody or antigen-binding fragment thereof that can be used in the context of the methods of the present disclosure comprises: (a) a first antigen-binding arm that binds MUC16 comprising the heavy chain complementarity determining regions (A-HCDR1, A-HCDR2 and A-HCDR3) of a heavy chain variable region (A-HCVR) comprising the amino acid sequence of SEQ ID NO: 16 and the light chain complementarity determining regions (A-LCDR1, A-LCDR2 and A-LCDR3) of a light chain variable region (A-LCVR) comprising the amino acid sequence of SEQ ID NO: 24; and (b) a second antigen-binding arm that binds CD28 comprising the heavy chain CDRs (B-HCDR1, B-HCDR2 and B-HCDR3) of a HCVR (B-HCVR) comprising an amino acid sequence of SEQ ID NO: 20, and the light chain CDRs (B-LCDR1, B-LCDR2 and B-LCDR3) of a LCVR (B-LCVR) comprising the amino acid sequence of SEQ ID NO: 24. According to certain embodiments, the A-HCDR1 comprises the amino acid sequence of SEQ ID NO: 17; the A-HCDR2 comprises the amino acid sequence of SEQ ID NO: 18; the A-HCDR3 comprises the amino acid sequence of SEQ ID NO: 19; the A-LCDR1 comprises the amino acid sequence of SEQ ID NO: 25; the A-LCDR2 comprises the amino acid sequence of SEQ ID NO: 26; the A-LCDR3 comprises the amino acid sequence of SEQ ID NO: 27; the B-HCDR1 comprises the amino acid sequence of SEQ ID NO: 21; the B-HCDR2 comprises the amino acid sequence of SEQ ID NO: 22; and the B-HCDR3 comprises the amino acid sequence of SEQ ID NO: 23; and the B-LCDR1 comprises the amino acid sequence of SEQ ID NO: 25; the B- LCDR2 comprises the amino acid sequence of SEQ ID NO: 26; the B-LCDR3 comprises the amino acid sequence of SEQ ID NO: 27. In yet other embodiments, the bispecific anti-MUC16/anti-CD28 antibody or antigen-binding fragment thereof comprises: (a) a first antigen-binding arm that binds MUC16 comprising a HCVR (A-HCVR) comprising SEQ ID NO: 16 and a LCVR (A-LCVR) comprising SEQ ID NO: 24; and (b) a second antigen-binding arm that binds CD28 comprising a HCVR (B-HCVR) comprising SEQ ID NO: 20, and a LCVR (B-LCVR) comprising SEQ ID NO: 24. In certain exemplary embodiments, the bispecific anti-MUC16 x CD28 antibody comprises a MUC16- binding arm comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 28 and a light chain comprising the amino acid sequence of SEQ ID NO: 30, and a CD28-binding arm comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 29 and a light chain comprising the amino acid sequence of SEQ ID NO: 30. An exemplary bispecific MUC16xCD28 antibody used in the context of the present methods is REGN5668. Bispecific Anti-MUC16 x Anti-CD3 Antibodies [0102] According to certain exemplary embodiments of the present disclosure, the methods comprise administering a therapeutically effective amount of a bispecific antibody comprising a first antigen-binding domain that specifically binds MUC16 and a second antigen-binding domain that specifically binds CD3. Such antibodies may be referred to herein as, e.g., "anti-MUC16/anti-CD3," or "anti-MUC16 x anti-CD3" or "MUC16 x CD3" bispecific antibodies, or other similar terminology. [0103] As used herein, the expression "bispecific antibody" refers to an immunoglobulin protein comprising at least a first antigen-binding domain and a second antigen-binding domain. In the context of the present disclosure, the first antigen-binding domain specifically binds a first antigen (e.g., MUC16), and the second antigen-binding domain specifically binds a second, distinct antigen (e.g., CD3). Each antigen-binding domain of a bispecific antibody comprises a heavy chain variable domain (HCVR) and a light chain variable domain (LCVR), each comprising three CDRs. In the context of a bispecific antibody, the CDRs of the first antigen-binding domain may be designated with the prefix "A" and the CDRs of the second antigen-binding domain may be designated with the prefix "B". Thus, the CDRs of the first antigen-binding domain may be referred to herein as A-HCDR1, A-HCDR2, and A-HCDR3; and the CDRs of the second antigen-binding domain may be referred to herein as B-HCDR1, B-HCDR2, and B-HCDR3. [0104] The first antigen-binding domain and the second antigen-binding domain are each connected to a separate multimerizing domain. As used herein, a "multimerizing domain" is any macromolecule, protein, polypeptide, peptide, or amino acid that has the ability to associate with a second multimerizing domain of the same or similar structure or constitution. In the context of the present disclosure, the multimerizing component is an Fc portion of an immunoglobulin (comprising a CH2-CH3 domain), e.g., an Fc domain of an IgG selected from the isotypes IgG1, IgG2, IgG3, and IgG4, as well as any allotype within each isotype group. [0105] Bispecific antibodies of the present disclosure typically comprise two multimerizing domains, e.g., two Fc domains that are each individually part of a separate antibody heavy chain. The first and second multimerizing domains may be of the same IgG isotype such as, e.g., IgG1/IgG1, IgG2/IgG2, IgG4/IgG4. Alternatively, the first and second multimerizing domains may be of different IgG isotypes such as, e.g., IgG1/IgG2, IgG1/IgG4, IgG2/IgG4, etc. [0106] Any bispecific antibody format or technology may be used to make the bispecific antibodies of the present disclosure. For example, an antibody or fragment thereof having a first antigen binding specificity can be functionally linked (e.g., by chemical coupling, genetic fusion, noncovalent association or otherwise) to one or more other molecular entities, such as another antibody or antibody fragment having a second antigen-binding specificity to produce a bispecific antibody. Specific exemplary bispecific formats that can be used in the context of the present disclosure include, without limitation, e.g., scFv-based or diabody bispecific formats, IgG-scFv fusions, dual variable domain (DVD)-Ig, Quadroma, knobs-into-holes, common light chain (e.g., common light chain with knobs-into-holes, etc.), CrossMab, CrossFab, (SEED)body, leucine zipper, Duobody, IgG1/IgG2, dual acting Fab (DAF)-IgG, and Mab₂ bispecific formats (see, e.g., Klein et al. 2012, mAbs 4:6, 1-11, and references cited therein, for a review of the foregoing formats). [0107] In the context of bispecific antibodies of the present disclosure, Fc domains may comprise one or more amino acid changes (e.g., insertions, deletions or substitutions) as compared to the wild-type, naturally occurring version of the Fc domain. For example, the disclosure includes bispecific antibodies comprising one or more modifications in the Fc domain that results in a modified Fc domain having a modified binding interaction (e.g., enhanced or diminished) between Fc and FcRn. In one embodiment, the bispecific antibody comprises a modification in a CH2 or a CH3 region, wherein the modification increases the affinity of the Fc domain to FcRn in an acidic environment (e.g., in an endosome where pH ranges from about 5.5 to about 6.0). Non-limiting examples of such Fc modifications are disclosed in US Patent Publication No.20150266966, incorporated herein in its entirety. [0108] The present disclosure also includes bispecific antibodies comprising a first CH3 domain and a second Ig CH3 domain, wherein the first and second Ig CH3 domains differ from one another by at least one amino acid, and wherein at least one amino acid difference reduces binding of the bispecific antibody to Protein A as compared to a bi-specific antibody lacking the amino acid difference. In one embodiment, the first Ig CH3 domain binds Protein A and the second Ig CH3 domain contains a mutation that reduces or abolishes Protein A binding such as an H95R modification (by IMGT exon numbering; H435R by EU numbering). The second CH3 may further comprise a Y96F modification (by IMGT; Y436F by EU). See, for example, US Patent No. 8,586,713. Further modifications that may be found within the second C_H3 include: D16E, L18M, N44S, K52N, V57M, and V82I (by IMGT; D356E, L358M, N384S, K392N, V397M, and V422I by EU) in the case of IgG1 antibodies; N44S, K52N, and V82I (IMGT; N384S, K392N, and V422I by EU) in the case of IgG2 antibodies; and Q15R, N44S, K52N, V57M, R69K, E79Q, and V82I (by IMGT; Q355R, N384S, K392N, V397M, R409K, E419Q, and V422I by EU) in the case of IgG4 antibodies. [0109] In certain embodiments, the Fc domain may be chimeric, combining Fc sequences derived from more than one immunoglobulin isotype. For example, a chimeric Fc domain can comprise part or all of a C_H2 sequence derived from a human IgG1, human IgG2 or human IgG4 C_H2 region, and part or all of a C_H3 sequence derived from a human IgG1, human IgG2 or human IgG4. A chimeric Fc domain can also contain a chimeric hinge region. For example, a chimeric hinge may comprise an "upper hinge" sequence, derived from a human IgG1, a human IgG2 or a human IgG4 hinge region, combined with a "lower hinge" sequence, derived from a human IgG1, a human IgG2 or a human IgG4 hinge region. A particular example of a chimeric Fc domain that can be included in any of the antibodies set forth herein comprises, from N- to C-terminus: [IgG4 C_H1]-[IgG4 upper hinge]- [IgG2 lower hinge]-[IgG4 CH2]-[IgG4 CH3]. Another example of a chimeric Fc domain that can be included in any of the antibodies set forth herein comprises, from N- to C-terminus: [IgG1 C_H1]- [IgG1 upper hinge]-[IgG2 lower hinge]-[IgG4 CH2]-[IgG1 CH3]. These and other examples of chimeric Fc domains or chimeric heavy chain constant regions that can be included in any of the antibodies of the present disclosure are described in US Patent Publication No.20140243504, which is herein incorporated in its entirety. Chimeric Fc domains and chimeric heavy chain constant regions having these general structural arrangements, and variants thereof, can have altered Fc receptor binding, which in turn affects Fc effector function. [0110] According to certain exemplary embodiments of the present disclosure, the bispecific anti- MUC16/anti-CD3 antibody, or antigen-binding fragment thereof comprises heavy chain variable regions (A-HCVR and B-HCVR), light chain variable regions (A-LCVR and B-LCVR), and/or complementarity determining regions (CDRs) comprising any of the amino acid sequences of the bispecific anti-MUC16/anti-CD3 antibodies as set forth in WO 2018/067331. In certain exemplary embodiments, the bispecific anti-MUC16/anti-CD3 antibody or antigen-binding fragment thereof that can be used in the context of the methods of the present disclosure comprises: (a) a first antigen- binding arm that binds MUC16 comprising the heavy chain complementarity determining regions (A-HCDR1, A-HCDR2 and A-HCDR3) of a heavy chain variable region (A-HCVR) comprising the amino acid sequence of SEQ ID NO: 31 and the light chain complementarity determining regions (A-LCDR1, A-LCDR2 and A-LCDR3) of a light chain variable region (A-LCVR) comprising the amino acid sequence of SEQ ID NO: 43; and (b) a second antigen-binding arm comprising the heavy chain CDRs (B-HCDR1, B-HCDR2 and B-HCDR3) of a HCVR (B-HCVR) comprising an amino acid sequence of SEQ ID NO: 35 or SEQ ID NO: 39, and the light chain CDRs (B-LCDR1, B- LCDR2 and B-LCDR3) of a LCVR (B-LCVR) comprising the amino acid sequence of SEQ ID NO: 43. According to certain embodiments, the A-HCDR1 comprises the amino acid sequence of SEQ ID NO: 32; the A-HCDR2 comprises the amino acid sequence of SEQ ID NO: 33; the A-HCDR3 comprises the amino acid sequence of SEQ ID NO: 34; the A-LCDR1 comprises the amino acid sequence of SEQ ID NO: 44; the A-LCDR2 comprises the amino acid sequence of SEQ ID NO: 45; the A-LCDR3 comprises the amino acid sequence of SEQ ID NO: 46; the B-HCDR1 comprises the amino acid sequence of SEQ ID NO: 36, or SEQ ID NO: 40; the B-HCDR2 comprises the amino acid sequence of SEQ ID NO: 37, or SEQ ID NO: 41; and the B-HCDR3 comprises the amino acid sequence of SEQ ID NO: 38, or SEQ ID NO: 42; and the B-LCDR1 comprises the amino acid sequence of SEQ ID NO: 44; the B-LCDR2 comprises the amino acid sequence of SEQ ID NO: 45; the B-LCDR3 comprises the amino acid sequence of SEQ ID NO: 46. In yet other embodiments, the bispecific anti-MUC16/anti-CD3 antibody or antigen-binding fragment thereof comprises: (a) a first antigen-binding arm comprising a HCVR (A-HCVR) comprising SEQ ID NO: 31 and a LCVR (A- LCVR) comprising SEQ ID NO: 43; and (b) a second antigen-binding arm comprising a HCVR (B- HCVR) comprising SEQ ID NO: 35 or SEQ ID NO: 39, and a LCVR (B-LCVR) comprising SEQ ID NO: 43. In certain exemplary embodiments, the bispecific anti-MUC16 x CD3 antibody comprises a MUC16-binding arm comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 47 and a light chain comprising the amino acid sequence of SEQ ID NO: 50, and a CD3-binding arm comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 48 and a light chain comprising the amino acid sequence of SEQ ID NO: 50. In certain exemplary embodiments, the bispecific anti-MUC16 x CD3 antibody comprises a MUC16-binding arm comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 47 and a light chain comprising the amino acid sequence of SEQ ID NO: 50, and a CD3-binding arm comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 49 and a light chain comprising the amino acid sequence of SEQ ID NO: 50. An exemplary bispecific MUC16xCD3 antibody used in the context of methods of the present disclosure is REGN4018 (ubamatamab). Combination Therapies [0111] The methods of the present disclosure, according to certain embodiments, comprise administering to the subject an anti-MUC16/anti-CD28 bispecific antibody in combination with an anti-PD-1 antibody or a bispecific anti-MUC16/anti-CD3 antibody. In certain embodiments, the methods of the present disclosure comprise administering the antibodies for additive or synergistic activity to treat a MUC16-expressing cancer, preferably ovarian cancer or endometrial cancer. As used herein, the expression "in combination with" means that the anti-MUC16/anti-CD28 bispecific antibody is administered before, after, or concurrent with the anti-PD-1 antibody or the anti- MUC16/anti-CD3 antibody. The term "in combination with" also includes sequential or concomitant administration of a bispecific anti-MUC16/anti-CD28 antibody and an anti-PD-1 antibody or a bispecific anti-MUC16/anti-CD3 antibody. For example, when administered "before" the bispecific anti-MUC16/anti-CD28 antibody, the anti-PD-1 antibody or the anti-MUC16/anti-CD3 antibody may be administered more than 150 hours, about 150 hours, about 100 hours, about 72 hours, about 60 hours, about 48 hours, about 36 hours, about 24 hours, about 12 hours, about 10 hours, about 8 hours, about 6 hours, about 4 hours, about 2 hours, about 1 hour, about 30 minutes, about 15 minutes or about 10 minutes prior to the administration of the bispecific anti-MUC16/anti-CD28 antibody. When administered "after" the bispecific anti-MUC16/anti-CD28 antibody, the anti-PD-1 antibody or the anti-MUC16/anti-CD3 antibody may be administered about 10 minutes, about 15 minutes, about 30 minutes, about 1 hour, about 2 hours, about 4 hours, about 6 hours, about 8 hours, about 10 hours, about 12 hours, about 24 hours, about 36 hours, about 48 hours, about 60 hours, about 72 hours, or more than 72 hours after the administration of the bispecific anti- MUC16/anti-CD28 antibody. Administration "concurrent" with the bispecific anti-MUC16/anti-CD28 antibody means that the anti-PD-1 antibody or the anti-MUC16/anti-CD3 antibody is administered to the subject in a separate dosage form within less than 5 minutes (before, after, or at the same time) of administration of the bispecific anti-MUC16/anti-CD28 antibody, or administered to the subject as a single combined dosage formulation comprising both the anti-PD-1 antibody or the anti- MUC16/anti-CD3 antibody, and the bispecific anti-MUC16/anti-CD28 antibody. [0112] In certain embodiments, the methods of the present disclosure comprise administration of a third therapeutic agent wherein the third therapeutic agent is an anti-cancer drug. In certain embodiments, the methods of the disclosure comprise administering an anti-PD-1 antibody or an anti-MUC16/anti-CD3 antibody, and an anti-MUC16/anti-CD28 bispecific antibody in combination with radiation therapy, surgery or other anti-cancer therapy to generate long-term durable anti- tumor responses and/or enhance survival of patients with a MUC16-expressing cancer. [0113] In some embodiments, the methods of the disclosure comprise administering radiation therapy prior to, concomitantly or after administering a bispecific anti-MUC16/anti-CD28 antibody in combination with an anti-PD-1 antibody or an anti-MUC16/anti-CD3 antibody to a cancer patient. For example, radiation therapy may be administered in one or more doses to tumor lesions after administration of one or more doses of the antibodies. In some embodiments, radiation therapy may be administered locally to a tumor lesion to enhance the local immunogenicity of a patient's tumor (adjuvinating radiation) and/or to kill tumor cells (ablative radiation) after systemic administration of the bispecific anti-MUC16/anti-CD28 antibody in combination with the anti-PD-1 antibody or the anti-MUC16/anti-CD3 antibody. Pharmaceutical Compositions and Administration [0114] The present disclosure includes methods which comprise administering a bispecific anti- MUC16/anti-CD28 antibody in combination with an anti-PD-1 antibody or a bispecific anti- MUC16/anti-CD3 antibody to a subject wherein the antibodies are contained within separate or a combined (single) pharmaceutical composition. The pharmaceutical compositions of the disclosure may be formulated with suitable carriers, excipients, and other agents that provide suitable transfer, delivery, tolerance, and the like. A multitude of appropriate formulations can be found in the formulary known to all pharmaceutical chemists: Remington's Pharmaceutical Sciences, Mack Publishing Company, Easton, Pa. These formulations include, for example, powders, pastes, ointments, jellies, waxes, oils, lipids, lipid (cationic or anionic) containing vesicles (such as LIPOFECTIN^TM), DNA conjugates, anhydrous absorption pastes, oil-in-water and water-in-oil emulsions, emulsions carbowax (polyethylene glycols of various molecular weights), semi-solid gels, and semi-solid mixtures containing carbowax. See also Powell et al. "Compendium of excipients for parenteral formulations" PDA (1998) J Pharm Sci Technol 52:238-311. [0115] Various delivery systems are known and can be used to administer the pharmaceutical composition of the disclosure, e.g., encapsulation in liposomes, microparticles, microcapsules, recombinant cells capable of expressing the mutant viruses, receptor mediated endocytosis (see, e.g., Wu et al., 1987, J. Biol. Chem.262: 4429-4432). Methods of administration include, but are not limited to, intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural, and oral routes. The composition may be administered by any convenient route, for example by infusion or bolus injection, or by injection, and may be administered together with other biologically active agents. [0116] A pharmaceutical composition of the present disclosure can be delivered subcutaneously or intravenously with a standard needle and syringe. In addition, with respect to subcutaneous delivery, a pen delivery device readily has applications in delivering a pharmaceutical composition of the present disclosure. Such a pen delivery device can be reusable or disposable. A reusable pen delivery device generally utilizes a replaceable cartridge that contains a pharmaceutical composition. Once all of the pharmaceutical composition within the cartridge has been administered and the cartridge is empty, the empty cartridge can readily be discarded and replaced with a new cartridge that contains the pharmaceutical composition. The pen delivery device can then be reused. In a disposable pen delivery device, there is no replaceable cartridge. Rather, the disposable pen delivery device comes prefilled with the pharmaceutical composition held in a reservoir within the device. Once the reservoir is emptied of the pharmaceutical composition, the entire device is discarded. [0117] Numerous reusable pen and autoinjector delivery devices have applications in the subcutaneous delivery of a pharmaceutical composition of the present disclosure. Examples include, but are not limited to AUTOPEN™ (Owen Mumford, Inc., Woodstock, UK), DISETRONIC™ pen (Disetronic Medical Systems, Bergdorf, Switzerland), HUMALOG MIX 75/25™ pen, HUMALOG™ pen, HUMALIN 70/30™ pen (Eli Lilly and Co., Indianapolis, IN), NOVOPEN™ I, II and III (Novo Nordisk, Copenhagen, Denmark), NOVOPEN JUNIOR™ (Novo Nordisk, Copenhagen, Denmark), BD™ pen (Becton Dickinson, Franklin Lakes, NJ), OPTIPEN™, OPTIPEN PRO™, OPTIPEN STARLET™, and OPTICLIK™ (sanofi-aventis, Frankfurt, Germany), to name only a few. Examples of disposable pen delivery devices having applications in subcutaneous delivery of a pharmaceutical composition of the present disclosure include, but are not limited to the SOLOSTAR™ pen (sanofi-aventis), the FLEXPEN™ (Novo Nordisk), and the KWIKPEN™ (Eli Lilly), the SURECLICK^TM Autoinjector (Amgen, Thousand Oaks, CA), the PENLET^TM (Haselmeier, Stuttgart, Germany), the EPIPEN (Dey, L.P.), and the HUMIRA^TM Pen (Abbott Labs, Abbott Park IL), to name only a few. [0118] In certain situations, the pharmaceutical composition can be delivered in a controlled release system. In one embodiment, a pump may be used. In another embodiment, polymeric materials can be used; see, Medical Applications of Controlled Release, Langer and Wise (eds.), 1974, CRC Pres., Boca Raton, Fla. In yet another embodiment, a controlled release system can be placed in proximity of the composition's target, thus requiring only a fraction of the systemic dose (see, e.g., Goodson, 1984, in Medical Applications of Controlled Release, supra, vol.2, pp.115- 138). Other controlled release systems are discussed in the review by Langer, 1990, Science 249:1527-1533. [0119] The injectable preparations may include dosage forms for intravenous, subcutaneous, intracutaneous and intramuscular injections, drip infusions, etc. These injectable preparations may be prepared by known methods. For example, the injectable preparations may be prepared, e.g., by dissolving, suspending or emulsifying the antibody or its salt described above in a sterile aqueous medium or an oily medium conventionally used for injections. As the aqueous medium for injections, there are, for example, physiological saline, an isotonic solution containing glucose and other auxiliary agents, etc., which may be used in combination with an appropriate solubilizing agent. The injection thus prepared is preferably filled in an appropriate ampoule. [0120] Advantageously, the pharmaceutical compositions for use described above are prepared into dosage forms in a unit dose suited to fit a dose of the active ingredients. Such dosage forms in a unit dose include, for example, a vial or a prefilled syringe. Administration Regimens [0121] The present disclosure includes methods comprising administering to a subject a bispecific anti-MUC16 x CD28 antibody in combination with an anti-PD-1 antibody or a bispecific anti-MUC16 x CD3 antibody at a dosing frequency of about four times a week, twice a week, once a week, once every two weeks, once every three weeks, once every four weeks, once every five weeks, once every six weeks, once every eight weeks, once every twelve weeks, or less frequently so long as a therapeutic response is achieved. Weekly dosing, or other dosing schedules such as once every two weeks, once every three weeks, once every four weeks, etc. (e.g., at any of the doses discussed herein), can be continued for a period of 1 week, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 216, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, or 52 weeks, for 13 months, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months, or more. In some cases, the weekly dosing may be converted to once every two weeks dosing, or to another dosing schedule as discussed herein, following any one of these periods of dosing, or any intermediate period of dosing falling within a range of the dosing periods discussed herein. [0122] According to certain embodiments of the present disclosure, multiple doses of a bispecific anti-MUC16/anti-CD28 antibody in combination with an anti-PD-1 antibody or a bispecific anti- MUC16/anti-CD3 antibody may be administered to a subject over a defined time course. The methods according to this aspect of the disclosure comprise sequentially administering to a subject one or more doses of a bispecific anti-MUC16/anti-CD28 antibody in combination with one or more doses of an anti-PD-1 antibody or a bispecific anti-MUC16/anti-CD3 antibody. As used herein, "sequentially administering" means that each dose of the antibody is administered to the subject at a different point in time, e.g., on different days separated by a predetermined interval (e.g., hours, days, weeks or months). The present disclosure includes methods which comprise sequentially administering to the patient a single initial dose of an antibody, followed by one or more secondary doses of the antibody, and optionally followed by one or more tertiary doses of the antibody. [0123] The terms "initial dose," "secondary doses," and "tertiary doses," refer to the temporal sequence of administration. Thus, the "initial dose" is the dose which is administered at the beginning of the treatment regimen (also referred to as the "baseline dose"); the "secondary doses" are the doses which are administered after the initial dose; and the "tertiary doses" are the doses which are administered after the secondary doses. The initial, secondary, and tertiary doses may all contain the same amount of the antibody (anti-PD-1 antibody or bispecific antibodies). In certain embodiments, however, the amount contained in the initial, secondary and/or tertiary doses varies from one another (e.g., adjusted up or down as appropriate) during the course of treatment. In certain embodiments, one or more (e.g., 1, 2, 3, 4, or 5) doses are administered at the beginning of the treatment regimen as "loading doses" followed by subsequent doses that are administered on a less frequent basis (e.g., "maintenance doses"). [0124] In one exemplary embodiment of the present disclosure, each secondary and/or tertiary dose is administered 1/2 to 14 (e.g., 1/2, 1, 11/2, 2, 21/2, 3, 31/2, 4, 41/2, 5, 51/2, 6, 61/2, 7, 71/2, 8, 81/2, 9, 91/2, 10, 101/2, 11, 111/2, 12, 121/2, 13, 131/2, 14, 141/2, or more) weeks after the immediately preceding dose. The phrase "the immediately preceding dose," as used herein, means, in a sequence of multiple administrations, the dose of a bispecific anti-MUC16/anti-CD28 (and anti- PD-1 antibody or bispecific anti-MUC16/anti-CD3 antibody) which is administered to a patient prior to the administration of the very next dose in the sequence with no intervening doses. [0125] The methods according to this aspect of the disclosure may comprise administering to a patient any number of secondary and/or tertiary doses of bispecific anti-MUC16/anti-CD28 antibody (and an anti-PD-1 antibody or bispecific anti-MUC16/anti-CD3 antibody). For example, in certain embodiments, only a single secondary dose is administered to the patient. In other embodiments, two or more (e.g., 2, 3, 4, 5, 6, 7, 8, or more) secondary doses are administered to the patient. Likewise, in certain embodiments, only a single tertiary dose is administered to the patient. In other embodiments, two or more (e.g., 2, 3, 4, 5, 6, 7, 8, or more) tertiary doses are administered to the patient. [0126] In embodiments involving multiple secondary doses, each secondary dose may be administered at the same frequency as the other secondary doses. For example, each secondary dose may be administered to the patient 1, 2 or 3 weeks (e.g., 1 week or 3 weeks) after the immediately preceding dose. Similarly, in embodiments involving multiple tertiary doses, each tertiary dose may be administered at the same frequency as the other tertiary doses. For example, each tertiary dose may be administered to the patient 1 to 4 weeks (e.g., 1 week or 3 weeks) after the immediately preceding dose. Alternatively, the frequency at which the secondary and/or tertiary doses are administered to a patient can vary over the course of the treatment regimen. The frequency of administration may also be adjusted during the course of treatment by a physician depending on the needs of the individual patient following clinical examination. [0127] In certain embodiments, one or more doses of a bispecific anti-MUC16/anti-CD28 antibody, an anti-PD-1 antibody, or bispecific anti-MUC16/anti-CD3 antibody are administered at the beginning of a treatment regimen as "induction doses" on a more frequent basis (twice a week, once a week, once in 2 weeks, or once in 3 weeks) followed by subsequent doses ("consolidation doses" or "maintenance doses") that are administered on the same or a less frequent basis (e.g., once in 4-12 weeks). [0128] The present disclosure includes methods comprising sequential administration of a bispecific anti-MUC16/anti-CD28 antibody in combination with an anti-PD-1 antibody or a bispecific anti-MUC16/anti-CD3 antibody to a patient to treat a MUC16-expressing cancer (e.g., ovarian cancer or endometrial cancer). In some embodiments, the present methods comprise administering one or more doses of a bispecific anti-MUC16/anti-CD28 antibody, optionally preceded by or followed by one or more doses of an anti-PD-1 antibody or a bispecific anti-MUC16/anti-CD3 antibody. In certain embodiments, the present methods comprise administering one or more doses of an anti-PD-1 antibody followed by one or more doses of a bispecific anti-MUC16/anti-CD28 antibody. In some embodiments, one or more doses of about 0.1 mg/kg to about 20 mg/kg (e.g., 100 to 600 mg) of an anti-PD-1 antibody may be administered followed by one or more doses of about 0.1 mg/kg to about 20 mg/kg (e.g., 0.01 to 600 mg) of the bispecific anti-MUC16/anti-CD28 antibody to inhibit tumor growth and/or to prevent tumor recurrence in a subject with a MUC16- expressing cancer (e.g., ovarian cancer or endometrial cancer). In certain embodiments, the present methods comprise administering one or more doses of a bispecific anti-MUC16/anti-CD3 antibody followed by one or more doses of a bispecific anti-MUC16/anti-CD28 antibody. In some embodiments, one or more doses of about 0.1 mg/kg to about 20 mg/kg (e.g., 100 to 600 mg) of a bispecific anti-MUC16/anti-CD3 antibody may be administered followed by one or more doses of about 0.1 mg/kg to about 20 mg/kg (e.g., 0.01 to 600 mg) of the bispecific anti-MUC16/anti-CD28 antibody to inhibit tumor growth and/or to prevent tumor recurrence in a subject with a MUC16- expressing cancer (e.g., ovarian cancer or endometrial cancer). In some embodiments, the bispecific antibody or the combination results in increased anti-tumor efficacy (e.g., greater inhibition of tumor growth, increased prevention of tumor recurrence as compared to an untreated subject or a subject administered with either antibody as monotherapy, respectively). Alternative embodiments of the disclosure pertain to concomitant administration of the antibodies, which are administered at a separate dosage at a similar or different frequency relative to the other antibodies. In some embodiments, the bispecific anti-MUC16/anti-CD28 antibody is administered before, after or concurrently with the anti-PD-1 antibody or the bispecific anti-MUC16/anti-CD3 antibody. In certain embodiments, the bispecific anti-MUC16/anti-CD28 antibody is administered as a single dosage formulation with the anti-PD-1 antibody, or with the bispecific anti-MUC16/anti-CD3 antibody. [0129] Other specific administration regimens for the bispecific anti-MUC16/anti-CD28 antibody in combination with the anti-PD-1 antibody or the bispecific anti-MUC16/anti-CD3 antibody are detailed in Figures 3 and 4, respectively. In some cases, a steroid (e.g., dexamethasone) or an IL- 6R antagonist (e.g., an anti-IL-6R antibody such as sarilumab or tocilizumab) may be administered with or prior to administration of a bispecific antibody (e.g., REGN4018) to minimize or prevent the risk or incidence of cytokine release syndrome (CRS) or infusion related reaction (IRR). Dosage [0130] The amount of bispecific anti-MUC16/anti-CD28 antibody, and anti-PD-1 antibody or bispecific anti-MUC16/anti-CD3 antibody, administered to a subject according to the methods of the present disclosure is, generally, a therapeutically effective amount. As used herein, the phrase "therapeutically effective amount" means an amount of antibody that results in one or more of: (a) a reduction in the severity or duration of a symptom of a cancer (e.g., ovarian cancer or endometrial cancer); (b) inhibition of tumor growth, or an increase in tumor necrosis, tumor shrinkage and/or tumor disappearance; (c) delay in tumor growth and development; (d) inhibition or retardation or stopping tumor metastasis; (e) prevention of recurrence of tumor growth; (f) increase in survival of a subject with cancer (e.g., ovarian cancer or endometrial cancer); and/or (g) a reduction in the use or need for conventional anti-cancer therapy (e.g., reduced or eliminated use of chemotherapeutic or cytotoxic agents) as compared to an untreated subject or a subject administered with either antibody as monotherapy. [0131] In the case of a bispecific anti-MUC16/anti-CD28 antibody, a therapeutically effective amount can be from about 0.01 milligrams (mg) to about 2000 mg, e.g., about 0.1 mg, about 0.2 mg, about 0.3 mg, about 0.5 mg, about 1 mg, about 3 mg, about 5 mg, about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 75 mg, about 100 mg, about 125 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1100 mg, about 1200 mg, about 1300 mg, about 1400 mg, about 1500 mg, about 1600 mg, about 1700 mg, about 1800 mg, about 1900 mg, about 2 g, about 2.5g, about 3 g, about 3.5 g, about 4 g, about 4.5 g, or about 5 g of the bispecific anti-MUC16/anti-CD28 antibody. In certain embodiments, 0.03 mg, 0.1 mg, 0.3 mg, 1 mg, 3 mg, 10 mg, 30 mg, 100 mg, or 300 mg of the bispecific anti-MUC16 x anti-CD28 antibody is administered (e.g., once weekly) to the subject to treat a MUC16-expressing cancer (e.g., ovarian cancer or endometrial cancer). [0132] In the case of an anti-PD-1 antibody, a therapeutically effective amount can be from about 0.05 mg to about 600 mg, e.g., about 0.05 mg, about 0.1 mg, about 1.0 mg, about 1.5 mg, about 2.0 mg, about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, about 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg, about 190 mg, about 200 mg, about 210 mg, about 220 mg, about 230 mg, about 240 mg, about 250 mg, about 260 mg, about 270 mg, about 280 mg, about 290 mg, about 300 mg, about 310 mg, about 320 mg, about 330 mg, about 340 mg, about 350 mg, about 360 mg, about 370 mg, about 380 mg, about 390 mg, about 400 mg, about 410 mg, about 420 mg, about 430 mg, about 440 mg, about 450 mg, about 460 mg, about 470 mg, about 480 mg, about 490 mg, about 500 mg, about 510 mg, about 520 mg, about 530 mg, about 540 mg, about 550 mg, about 560 mg, about 570 mg, about 580 mg, about 590 mg, or about 600 mg, of the anti-PD-1 antibody. In certain embodiments, 300 mg to 400 mg of the anti-PD-1 antibody is administered (e.g., once every three weeks) to the subject in combination with the bispecific anti-MUC16/anti-CD28 antibody to treat a MUC16-expressing cancer (e.g., ovarian cancer or endometrial cancer). In certain embodiments, 350 mg of an anti-PD-1 antibody is administered (e.g., once every three weeks) to the subject in combination with the bispecific anti- MUC16/anti-CD28 antibody to treat a MUC16-expressing cancer (e.g., ovarian cancer or endometrial cancer). [0133] In the case of a bispecific anti-MUC16/anti-CD3 antibody, a therapeutically effective amount can be from about 0.01 milligrams (mg) to about 2000 mg, e.g., about 0.1 mg, about 0.2 mg, about 0.3 mg, about 0.5 mg, about 1 mg, about 3 mg, about 5 mg, about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 75 mg, about 100 mg, about 125 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1100 mg, about 1200 mg, about 1300 mg, about 1400 mg, about 1500 mg, about 1600 mg, about 1700 mg, about 1800 mg, about 1900 mg, about 2 g, about 2.5g, about 3 g, about 3.5 g, about 4 g, about 4.5 g, or about 5 g of the bispecific anti-MUC16/anti-CD3 antibody. In certain embodiments, 0.03 mg, 0.1 mg, 0.3 mg, 1 mg, 3 mg, 10 mg, 30 mg, 100 mg, 300 mg, 600 mg, or 900 mg of the bispecific anti-MUC16 x anti-CD3 antibody is administered (e.g., once weekly) to the subject to treat a MUC16-expressing cancer (e.g., ovarian cancer or endometrial cancer). [0134] In some embodiments, the methods of the present disclosure for treating a MUC16- expressing cancer (e.g., ovarian cancer or endometrial cancer) include a dosing regimen in which REGN5668 is administered to a subject in need thereof weekly at a dose of 0.1 mg, 0.3 mg, 1 mg, 3 mg, 10 mg, 30 mg, 100 mg, 300 mg, or 1000 mg, and cemiplimab is administered to the subject at a dose of 350 mg once every three weeks beginning in week four (i.e., following the first three weekly doses of REGN5668) of the dosing regimen. [0135] In some embodiments, the methods of the present disclosure for treating a MUC16- expressing cancer (e.g., ovarian cancer or endometrial cancer) include a dosing regimen in which REGN4018 is administered to a subject in need thereof at a dose of 1 mg in week 1 of the dosing regimen, REGN4018 is administered to the subject in two doses of 10 mg each in week 2 of the dosing regimen (e.g., on two consecutive days), REGN4018 is administered to the subject at a dose of 250 mg in week 3 and subsequent weeks of the dosing regimen, REGN5668 is administered to the subject at a dose of 0.03 mg, 0.1 mg or 0.3 mg in week 5 of the dosing regimen, and REGN5668 is administered to the subject at a dose of 0.1 mg, 0.3 mg, or 1 mg in week 6 and subsequent weeks of the dosing regimen. [0136] In some embodiments, the methods of the present disclosure for treating a MUC16- expressing cancer (e.g., ovarian cancer or endometrial cancer) include a dosing regimen in which REGN4018 is administered to a subject in need thereof at a dose of 1 mg in week 1 of the dosing regimen, REGN4018 is administered to the subject in two doses of 10 mg each in week 2 of the dosing regimen (e.g., on two consecutive days), REGN4018 is administered to the subject at a dose of 250 mg in week 3 and subsequent weeks of the dosing regimen, and REGN5668 is administered to the subject at a dose of 10 mg, 100 mg, 300 mg, or 1000 mg in week 5 and subsequent weeks of the dosing regimen. [0137] The amount of bispecific anti-MUC16/anti-CD28 antibody, and the anti-PD-1 antibody or the bispecific anti-MUC16/anti-CD3 antibody contained within the individual doses may be expressed in terms of milligrams of antibody per kilogram of subject body weight (i.e., mg/kg). In certain embodiments, the antibodies used in the methods of the present disclosure may be administered to a subject at a dose of about 0.0001 to about 100 mg/kg of subject body weight. For example, the bispecific anti-MUC16/anti-CD28 antibody may be administered at a dose of about 0.1 mg/kg to about 20 mg/kg of a patient's body weight, the anti-PD-1 antibody may be administered at dose of about 0.1 mg/kg to about 20 mg/kg of a patient's body weight, and the bispecific anti- MUC16/anti-CD3 antibody may be administered at a dose of about 0.1 mg/kg to about 20 mg/kg of a patient's body weight. [0138] A summary of the sequences and the corresponding SEQ ID NOs referenced herein is shown in Table 1, below. Table 1: Summary of Sequences SEQ ID NO: Description BISPECIFIC MUC16 x CD28 ANTIBODIES

27 Anti-MUC16 and Anti-CD28 LCDR3 (-002) 28 Anti-MUC16 Heavy Chain (-002)

58 Anti-PD-1 LCDR3 59 Anti-PD-1 Heavy Chain

[0139] The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how to make and use the methods and compositions of the disclosure, and are not intended to limit the scope of what the inventors regard as their disclosure. Efforts have been made to ensure accuracy with respect to numbers used (e.g., amounts, temperature, etc.) but some experimental errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, molecular weight is average molecular weight, temperature is in degrees Centigrade, and pressure is at or near atmospheric. Example 1: Generation of Bispecific Antibodies that Bind MUC16 and CD28 [0140] The present disclosure provides methods of use of bispecific antigen-binding molecules that bind CD28 and MUC16; such bispecific antigen-binding molecules are also referred to herein as “anti-MUC16/anti-CD28 or anti-MUC16xCD28 bispecific molecules.” The anti-MUC16 portion of the anti-MUC16/anti-CD28 bispecific molecule is useful for targeting tumor cells that express MUC16 (also known as CA-125), and the anti-CD28 portion of the bispecific molecule is useful for activating T-cells. The simultaneous binding of MUC16 on a tumor cell and CD28 on a T-cell facilitates directed killing (cell lysis) of the targeted tumor cell by the activated T-cell. [0141] Bispecific antibodies comprising an anti-MUC16-specific binding domain and an anti- CD28-specific binding domain were constructed using standard methodologies, wherein the anti- MUC16 antigen binding domain and the anti-CD28 antigen binding domain each comprise different, distinct HCVRs paired with a common LCVR. In exemplified bispecific antibodies, the molecules were constructed utilizing a heavy chain from an anti-CD28 antibody, a heavy chain from an anti- MUC16 antibody and a common light chain. [0142] Exemplified bispecific antibodies were manufactured having a modified (chimeric) IgG4 Fc domain (BSMUC16/CD28-001 and BSMUC16/CD28-002) as set forth in US Patent Application Publication No. US20140243504A1, published on August 28, 2014. The corresponding CDR sequences and full-length heavy and light chain sequences are identified in Table 1. An exemplary bispecific antibody with the VRs and CDRs of BSMUC16/CD28-001 is REGN5668 (also referred to as “mAb1” herein). REGN5668 comprises a first heavy chain of SEQ ID NO: 13; a second heavy chain of SEQ ID NO: 14 and a common light chain of SEQ ID NO: 15. [0143] A summary of the component parts of the antigen-binding domains of the various anti- MUC16xCD28 bispecific antibodies constructed is set forth in Table 2. Table 2: Summary of Component Parts of Anti-MUC16xCD28 Bispecific Antibodies Anti-MUC16 Anti-CD28 Antigen-Binding Antigen-Binding Common n ) )

Example 2: Generation of Bispecific Antibodies that Bind MUC16 and CD3 [0144] The present disclosure provides methods of use of bispecific antigen-binding molecules that bind CD3 and MUC16; such bispecific antigen-binding molecules are also referred to herein as “anti-MUC16/anti-CD3 or anti-MUC16xCD3 bispecific molecules.” The anti-MUC16 portion of the anti-MUC16/anti-CD3 bispecific molecule is useful for targeting tumor cells that express MUC16 (also known as CA-125), and the anti-CD3 portion of the bispecific molecule is useful for activating T-cells. The simultaneous binding of MUC16 on a tumor cell and CD3 on a T-cell facilitates directed killing (cell lysis) of the targeted tumor cell by the activated T-cell. [0145] Bispecific antibodies comprising an anti-MUC16-specific binding domain and an anti-CD3- specific binding domain were constructed using standard methodologies, wherein the anti-MUC16 antigen binding domain and the anti-CD3 antigen binding domain each comprise different, distinct HCVRs paired with a common LCVR. In exemplified bispecific antibodies, the molecules were constructed utilizing a heavy chain from an anti-CD3 antibody, a heavy chain from an anti-MUC16 antibody and a common light chain. [0146] Exemplified bispecific antibodies were manufactured having a modified (chimeric) IgG4 Fc domain (BSMUC16/CD3-001 and BSMUC16/CD3-002) as set forth in US Patent Application Publication No. US20140243504A1, published on August 28, 2014. An exemplary bispecific antibody comprising the VRs and CDRs of BSMUC16/CD3-001 is REGN4018 (also known as ubamatamab; referred to as “mAb2” herein). REGN4018 comprises a first heavy chain of SEQ ID NO: 47, a second heavy chain of SEQ ID NO: 48 and a common light chain of SEQ ID NO: 50. [0147] A summary of the component parts of the antigen-binding domains of the various anti- MUC16xCD3 bispecific antibodies constructed is set forth in Table 3. The corresponding CDR sequences and full-length heavy and light chain sequences are identified in Table 1. Table 3: Summary of Component Parts of Anti-MUC16xCD3 Bispecific Antibodies Anti-MUC16 Anti-CD3 Antigen-Binding Antigen-Binding Common n ) )

Example 3: A Phase 1/2 Study of a Bispecific Anti-MUC16 x Anti-CD28 Antibody Administered in Combination with an Anti-PD-1 Antibody or a Bispecific Anti-MUC16 x Anti- CD3 Antibody in Patients with Progressive, Recurrent or Refractory Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer [0148] This is a phase 1/2, first-in-human, open-label, multicenter, dose-escalation study with cohort expansion of the safety, tolerability, efficacy, and pharmacokinetics of mAb1, a MUC16 x CD28 bispecific antibody, administered with a monotherapy lead-in, in combination with the PD-1 antibody cemiplimab (Module 1) and, separately, in combination with the MUC16 x CD3 bispecific antibody mAb2 (Module 2) in patients with recurrent ovarian cancer. The patient population includes patients with progressive, recurrent, or refractory ovarian cancer, fallopian tube cancer, or primary peritoneal cancer with serum CA-125 levels ≥2x upper limit of normal (ULN), who have received at least 1 line of platinum-based therapy, and for whom there are no standard therapies likely to convey clinical benefit. [0149] Study Objectives [0150] The primary objectives of the study are: (i) to assess the safety, tolerability, and pharmacokinetics (PK) of mAb1 (REGN5668) alone and in separate combinations with cemiplimab or mAb2 (REGN4018), in order to determine a maximally tolerated dose(s) (MTD) or recommended phase 2 dose(s) (RP2D) of mAb1 in these combinations (in the dose escalation phase); and (ii) to assess the preliminary efficacy of mAb1 in combination with cemiplimab or mAb2, (separately by cohort and combination) as determined by the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (in the dose expansion phase). [0151] The secondary objectives of the study are: (i) to assess the preliminary efficacy of mAb1 in combination with cemiplimab or mAb2 (separately by cohort and combination) as determined by objective response rate (ORR) by RECIST 1.1 (in the dose escalation phase); (ii) to characterize the safety profile in each expansion cohort (in the dose expansion phase); (iii) to characterize the PK of mAb1 in combination with cemiplimab or mAb2 (separately by cohort and combination) (in the dose expansion phase); (iv) to assess preliminary efficacy of mAb1 in combination with cemiplimab or mAb2 (separately by cohort and combination) as measured by ORR based on immune based therapy RECIST (iRECIST), best overall response (BOR), duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS) based on RECIST 1.1 and iRECIST (in both the dose escalation and dose expansion phases); (v) to assess changes in CA-125 level from baseline after treatment with mAb1 in combinations with cemiplimab or mAb2 (separately by cohort and combination) (in both the dose escalation and dose expansion phases); and (vi) immunogenicity of mAb1, alone and in combinations with cemiplimab or mAb2 (in both the dose escalation and dose expansion phases). [0152] The exploratory objectives of the study are: • To evaluate biomarkers that may correlate with mechanism of action, increase understanding of disease/on-target activity, observed toxicity, and potential anti-tumor activity, or markers that may be predictors of efficacy and/or safety, which may include but are not limited to: • MUC16 and programmed cell death-ligand 1 (PD-L1) expression in tumors • Intratumoral and circulating immune cell populations • Plasma cytokines, chemokines and other circulating proteins • Intratumoral gene/transcript expression, tumor and circulating gene mutational burden • Where possible, to evaluate the relationship between exposure and efficacy, biomarker and safety endpoints • To assess overall survival (OS) [0153] Study Design [0154] This is a phase 1/2 dose-escalation study with cohort expansion of the safety, tolerability, efficacy, and pharmacokinetics of mAb1, REGN5668, a MUC16xCD28 bispecific antibody, administered with a monotherapy lead-in, in combination with the PD-1 antibody cemiplimab (Module 1) and, separately, in combination with the MUC16xCD3 bispecific antibody, REGN4018, mAb2 (Module 2) in patients with recurrent ovarian cancer. The patient population will include patients with progressive, recurrent, or refractory ovarian cancer, fallopian tube cancer, or primary peritoneal cancer with serum CA-125 levels ≥2x upper limit of normal (ULN), who have received at least 1 line of platinum-based therapy, and for whom there are no standard therapies likely to convey clinical benefit. The study contains separate dose escalation modules and separate dose expansion cohorts for each combination. Each module contains a series of dose escalation cohorts. Modules will have a staggered start beginning with Module 1. [0155] Module 1: mAb1 in combination with cemiplimab - during dose escalation, patients will receive a 3- to 4-week monotherapy lead-in of mAb1 (cycle 0) at the assigned dose level (DL) intravenously (IV) weekly (QW), followed by combination therapy of mAb1 at the assigned DL IV QW and cemiplimab 350 mg IV once every three weeks (Q3W) (cycle 1 and beyond). [0156] Combination therapy with cemiplimab will begin on cycle 1 day 1 after completion of a mAb1 monotherapy lead-in cycle (cycle 0). Cycle 1 will be initiated only after the patient has 1) received at least 3 doses of mAb1, and 2) does not develop cytokine release syndrome (CRS) in the last mAb1 infusion of cycle 0 according to updated ASTCT criteria and after sponsor review of safety data. The starting date of cycle 1 day 1 will be no earlier than 21 days from cycle 0 day 1 and no later than 28 days from cycle 0 day 1. Thus, the length of cycle 0 may differ between patients but will be no more than 4 weeks. [0157] Treatment for each patient will continue as established in cycle 1 for the respective dose level until disease progression or intolerable toxicity occurs. [0158] The purpose of the dose escalation cohorts in Module 1 is to evaluate mAb1 monotherapy and identify an MTD or RP2D of mAb1 for testing in combination with cemiplimab (in the Module 1 dose expansion cohort). The dose-limiting toxicity (DLT) period for determining safety for dose escalation in Module 1 is defined as 42 days (or up to 49 days if initiation of combination therapy is delayed) starting with cycle 0 day 1. The intent of the DLT observation period in Module 1 is to monitor the safety and tolerability of at least the first 3 doses of mAb1 in monotherapy and the first 3 weeks of combination therapy with cemiplimab. [0159] Additional cohorts may assess whether the mAb1 monotherapy lead-in may be shortened or removed prior to Module 1 expansion. [0160] The primary purpose of the Module 1 dose expansion cohort will be to assess the preliminary efficacy of the mAb1 RP2D in combination with cemiplimab, using a Simon’s 2-stage design. Dose escalation will proceed as shown in Table 4. Table 4: Dose Escalation for Module 1 (mAb1 and cemiplimab) Dose Level mAb1 Cemiplimab

Dose Level mAb1 Cemiplimab M1-DL1 0.3 mg 350 mg

[0161] Module 2: mAb1 in combination with mAb2 - module 2 will begin after at least 2 dose levels in Module 1 have been tolerated. [0162] Patients will receive 4 to 5-weeks of monotherapy of mAb2 IV QW (cycle 0; including initial, transitional, and at least 2 full doses) followed by combination therapy of mAb1 with full dose mAb2. For each patient, combination therapy will begin after the monotherapy lead-in of mAb2 is well tolerated (i.e., no CRS per updated ASTCT criteria in the last mAb2 monotherapy dose given). The DLT period in Module 2 is defined as 21 days (or up to 28 days if the administration of full dose mAb1 is delayed) after the start of mAb1 administration (beginning on cycle 1 day 1) (i.e., it will not include the mAb2 monotherapy lead-in [cycle 0]). The intent of the DLT observation period for dose escalation in Module 2 is to monitor the safety and tolerability of the first 3 weeks of the combination of mAb2 and mAb1. [0163] The primary purpose of the Module 2 dose expansion cohort (described in greater detail below) will be to assess the preliminary efficacy of the mAb1 RP2D in combination with mAb2, using a Simon’s 2-stage design. Dose escalation will proceed as shown in Table 5. Table 5: Dose Escalation for Module 2 (mAb1 and mAb2) Dose Level mAb2 mAb2 mAb2 mAb1 mAb1

M2-DL9 1 mg 20 mg 250 mg 300 mg M2-DL10 1 mg 20 mg 250 mg 1000 mg

initially be enrolled at each DL (except for the first DL in Modules 1 and 2). The following rules will be used to assign a DL to the next group of patients: • If the number of patients who experience a DLT at the current DL is less than or equal to the escalation boundary specified, dose will be escalated to the next higher DL. If DLT rates in the first group of patients allow for dose escalation, additional DLT-evaluable patients may be added to the current DL before a decision is made to escalate the dose in order to further evaluate safety. • If the number of patients who experience a DLT at the current DL is greater than or equal to the de-escalation boundary but less than elimination boundary, dose will be de-escalated to the next lower DL. • If the number of patients who experience a DLT at the current DL is greater than or equal to the elimination boundary, the current and all higher DLs will be eliminated from the trial to prevent treating any further patients at these doses. When a dose is eliminated, the dose will be de-escalated to the next lower DL for subsequent subjects. • If none of the actions (i.e., escalation, de-escalation or elimination) are triggered, additional patients may be treated at the current DL. • If the accumulated number of patients treated at the current DL reaches 12, escalation may be stopped to select the MTD/ presumptive RP2D per clinical judgment. [0165] The DLT criteria take into consideration 1) Which normal tissues have MUC16 expression, 2) toxicology findings in cynomolgus monkeys treated with monotherapy cemiplimab, mAb1 or mAb2, mAb1 in combination with mAb2, and mAb1 in combination with cemiplimab and mAb2, 3) adverse events in patients treated with mAb2 and/or with cemiplimab in clinical studies or post- marketing use, and 4) experiences with other bispecific and costimulatory antibodies in humans. The same DLT criteria are used in both modules, although the timing and duration of the DLT period differ and are based on the sequencing of study drugs in each module. [0166] During dose escalation, additional data may be collected on safety, efficacy, and other biological information to better inform expansion dose selection. To collect such data, up to 6 additional patients may be enrolled in up to 2 dose levels per module. While adverse events observed in these patients will be considered in dose escalation decisions, these additional patients will not formally be part of the algorithm for determining the MTD. [0167] Dose Expansion for Module 1 and Module 2 - after identification of the mAb1 MTD/RP2Ds of a combination regimen, 50-patient expansion cohorts will be opened for that combination regimen using a Simon 2-stage design (n=20 patients in stage 1; n=30 patients in stage 2). The enrollment of stage 2 for each expansion cohort will occur only if the minimum number of tumor responses is observed at stage 1. Dose levels of mAb1 may differ between Module 1 and 2 expansion cohorts. [0168] If a patient develops grade ≥2 CRS at any DL of mAb1, a strategy of utilizing premedications and possibly a transitional dose between the initial and full doses will be used in subsequent patients in the same DL and subsequent DLs per the following guidance: • Module 1 only: In the case of grade ≥2 CRS with the initial or subsequent doses, premedication with antihistamines and acetaminophen (and optionally corticosteroids) may be used for subsequent patients enrolled at that DL. • Module 1 only: If dosing is tolerated during the monotherapy lead-in cycle, but grade ≥2 CRS is first observed upon combination with cemiplimab and persists in the setting of premedication, then the first dose of mAb1 given in combination with cemiplimab (i.e., cycle 1 day 1) may be limited to the highest dose of mAb1 administered in combination with cemiplimab without the development of CRS. For patients in higher DL cohorts, a transitional dose that is considered to be tolerable at the time may be administered before administering the full dose for the DL. Example: if during the monotherapy lead-in for Module 1 at DL3, 3 mg is administered without CRS, but 3 mg administered in combination with cemiplimab in cycle 1 day 1 is associated with grade ≥2 CRS, then subsequent patients at DL3 will be administered 1 mg on cycle 1 day 1 for their first combination dose with cemiplimab, and the following doses will be administered at 3 mg. • Module 2 only: Premedication with antihistamines and acetaminophen (and optionally corticosteroids) is required. If grade ≥2 CRS persists in the setting of premedication with the initial dose at any DL in Module 2, then the initial mAb1 dose for subsequent study patients may be limited to the highest dose administered without the development of more than mild/moderate IRR/CRS. Example: if DL4 (0.3 mg) is associated with severe IRR/CRS at cycle 1 day 1, but DL3 (0.1 mg dose) was tolerated without more than mild/moderate CRS, the subsequent patients in DL4 and subsequent DLs may receive 0.1 mg for the initial dose followed by 0.3 mg for the subsequent dose. Subsequent cohorts may also receive 0.1 mg for the initial dose, even as the DL continues to escalate. For patients in higher DL cohorts, a transitional dose of mAb1 that is considered to be tolerable at the time may be administered before administering the full dose of mAb1 for the DL. [0169] Study Duration [0170] The total duration of study participation for each patient will vary based on the occurrence of 1 or more of the following: disease progression, intolerable AEs, withdrawal of consent, or study withdrawal criterion is met. The study will consist of 4 periods, including: • Screening period (up to 28 days) • Monotherapy lead-in − Module 1: mAb1 lead-in 3 to 4 weeks (21 to 28 days) − Module 2: mAb2 lead-in 4 to 5 weeks (28 to 35 days) • Combination therapy treatment period (variable duration) • Follow-up period (approximately 90 days from last dose for patients who discontinue due to disease progression or toxicity, or who start another therapy; approximately 168 days from last dose for patients who discontinue in the setting of complete response) [0171] Study Population [0172] A maximum of 412 patients will be enrolled for the study (up to 212 patients in the dose escalation phase, and up to 200 patients in the dose expansion phase). [0173] The study population includes patients with progressive, recurrent, or refractory ovarian cancer, fallopian tube cancer, or primary peritoneal cancer with serum CA-125 levels ≥2 x ULN, who have received at least 1 line of platinum-based therapy, and for whom there are no standard therapies likely to convey clinical benefit. [0174] Inclusion Criteria: A patient must meet the following criteria to be eligible for inclusion in the study: 1. Is a woman ≥18 years of age. 2. Has histologically or cytologically confirmed diagnosis of advanced epithelial ovarian cancer (except carcinosarcoma), primary peritoneal, or fallopian tube cancer that has received at least 1 line of platinum-based systemic therapy and has: a. Been treated with or is intolerant to available standard-of-care therapy likely to convey clinical benefit (e.g., PARP therapy for BRCAm patients or bevacizumab as appropriate) b. Documented relapse or progression on or after the most recent line of therapy 3. In dose escalation, patients will provide either newly obtained biopsy (newly obtained biopsies at screening are required unless medically inappropriate and discussed with medical monitor). If fresh biopsies are not appropriate, and after sponsor approval, archived tumor tissue in dose escalation is acceptable. In dose expansion, patients will provide a fresh tumor biopsy in screening and on treatment. Hence, in expansion cohorts, only patients who (in the opinion of the investigator) have accessible lesions that can be biopsied without significant risk to the patient are eligible. 4. Expansion cohorts only: Has at least 1 lesion that is measurable by RECIST 1.1. Tumor lesions in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions after radiation. 5. Has a serum CA-125 level ≥2x ULN (in screening) 6. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 7. Has adequate organ and bone marrow function documented by: a. Hemoglobin ≥8.5 g/dL. b. Absolute neutrophil count ≥1.5x 10⁹/L. c. Platelet count ≥75 x 10⁹/L. d. Serum creatinine ≤1.5 x ULN or estimated glomerular filtration rate >50 mL/min/1.73m² (according to MDRD or CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation). A 24-hour urine creatinine collection may substitute for the calculated creatinine clearance to meet eligibility criteria. e. Adequate hepatic function: a. Total bilirubin ≤1.5 x ULN (≤3 x ULN if tumor liver involvement or known Gilbert’s Syndrome) b. Aspartate Aminotransferase (AST) ≤2.5 x ULN (≤5 x ULN if tumor liver involvement) c. Alanine Aminotransferase (ALT) ≤2.5 x ULN (≤5 x ULN if tumor liver involvement) d. Alkaline Phosphatase (ALP) ≤2.5 x ULN (≤5 x ULN if tumor liver or bone involvement) NOTES: In patients with tumor liver involvement if levels of AST ≥3 x ULN or ALT ≥3 x ULN, and bilirubin levels ≥2 x ULN will be excluded regardless of the above criteria. 8. Has a life expectancy of at least 3 months. 9. Is willing and able to comply with clinic visits and study-related procedures and requirements. 10. Is willing and able to provide informed consent as specified by health authorities and institutional guidelines. 11. Is able to understand and complete study-related questionnaires, if applicable. [0175] Exclusion Criteria: A patient who meets any of the following criteria will be excluded from the study: 1. Is currently receiving treatment in another study. Has participated in a study of an investigational agent (except biologics and/or immunotherapy) or an investigational device within 4 weeks of first dose of study drug. Has received treatment with an approved systemic therapy (except biologics and/or immunotherapy) within 3 weeks or has not yet recovered (i.e., grade ≤ 1 or baseline) from any acute toxicities except for chronic grade ≤2 neuropathy, chronic hearing loss, or laboratory changes as described in inclusion criteria. Has received any previous systemic biologic therapy within 5 half-lives of first dose of study drug or 28 days, whichever is longer, except as follows: Patients previously treated with cetuximab, rituximab, or other non-immunomodulatory antibodies with half-lives longer than 7 days are permitted after a discussion with the sponsor if at least 3 half-lives have elapsed since last treatment. Note: Patients previously treated with bevacizumab are permitted if there was no history of bowel perforation or wound complications on bevacizumab AND the last dose was >30 days from the first dose of REGN5668 (in Module 1) or REGN4018 (in Module 2). Prior anti-cancer immunotherapy as described below: • Recent anti-PD-1/PD-L1 therapy (within 5 half-lives of first dose of study therapy) • Received CAR-T within 30 days of first dose of study drug • Has not recovered (i.e., grade ≤1 or baseline) from immune-mediated adverse events of grade 2 or higher at least 1 month prior to initiation of study drug are excluded. Endocrinopathies adequately managed with hormone replacement and vitiligo are not exclusionary Has received radiation therapy or major surgery within 14 days of first administration of study drug or has not recovered (i.e., grade ≤1 or baseline) from adverse events, except for chronic grade ≤2 neuropathy or laboratory changes as described in inclusion criteria. Has had another malignancy within the last 5 years that is progressing, requires active treatment, or has a high likelihood of recurrence. Exceptions include: • Non-melanoma skin cancer that has undergone potentially curative therapy • In situ cervical carcinoma • Any tumor that has been deemed to be effectively treated with definitive local control (with or without continued adjuvant hormonal therapy). Prior treatment with a MUC16-targeted therapy. Expansion cohorts only: More than 4 prior lines of cytotoxic chemotherapy (including antibody drug conjugates). Note: In dose-escalation cohorts there is no maximum limit on prior lines of therapy. Has any condition that requires ongoing/continuous corticosteroid therapy (>10 mg prednisone/day or anti-inflammatory equivalent) within 1 week prior to the first dose of study drug. Physiologic replacement doses are allowed even if they are >10 mg of prednisone/day or equivalent, provided they are not being administered for immunosuppressive intent. Inhaled, intranasal, or topical steroids are permitted, provided that they are not for treatment of an autoimmune disorder. Note: Patients who require a brief course of steroids (up to 2 days in the week before enrollment) may be enrolled in the study. Has ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments. The following are not exclusionary: vitiligo, childhood asthma that has resolved, endocrinopathies (such as hypothyroidism or type 1 diabetes) that require only hormone replacement, or psoriasis that does not require systemic treatment. Has untreated or active primary brain tumor, CNS metastases, leptomeningeal disease, or spinal cord compression. Exception: Patients with previously treated central nervous system metastases or spinal cord compression may participate provided: • No evidence of progression for at least 4 weeks prior to the first dose of study drug, and any neurologic symptoms have returned to baseline • No evidence of new or enlarging central nervous system metastases • No requirement for systemic corticosteroids for management of central nervous system metastases or spinal cord compression within 2 weeks prior to the first dose of study drug Has encephalitis, meningitis, organic brain disease (e.g., Parkinson’s disease) or uncontrolled seizures in the year prior to first dose of study drug. Has a clinically significant abnormal ECG reading, and/or the following criteria: • QTc [Fredericia] interval>470 msec − In cases of asymptomatic prolonged QTc interval (>470 msec), the ECG can be repeated up to 2 times. If subsequent QTc interval is <470 msec, the patient may be enrolled only after review and approval by a cardiologist. • Evidence of Second-Degree AV block type II (Mobitz type II) or AV block type III (complete heart block) • Has a history of any clinically significant arrhythmia including atrial fibrillation or implantation of a pacemaker or defibrillator Has any history of the following: • Myocarditis • Clinically significant valvular heart disease (generally moderate or greater in severity), uncorrected with surgical or transcatheter valve procedure Has history of clinically significant cardiovascular disease including but not limited to the following, within 6 months prior to screening: • Myocardial infarction • Unstable angina • Stroke or transient ischemic attack • Peripheral arterial disease event • Heart failure (NYHA class III and IV or ACC/AHA heart failure classification C or D) • Signs or symptoms of active angina or heart failure, including left ventricular ejection fraction (LVEF) less than 50% as measured by echocardiogram at baseline. In cases of LVEF 45-50% in absence of clinical symptoms, after review and clearance by a cardiologist, the patient may be enrolled. Has moderate to large pericardial effusion (e.g., >approximately 100 mL) as measured by echocardiogram at baseline. Baseline serum troponin above institutional upper limit of normal. In cases of minimally elevated troponin in absence of clinical symptoms, and after clearance by a cardiologist, the patient may be enrolled. Has a known history of, or any evidence of, interstitial lung disease or active, non-infectious pneumonitis within 5 years prior to the first dose of study drug. A history of radiation pneumonitis in a radiation field is permitted. Has moderate to large pleural effusion at baseline that may require thoracentesis within the next 4 weeks due to size or rate of enlargement. Pre-existing chest tube is acceptable, if patient meets all other inclusion/exclusion criteria. Requires 2 or more therapeutic paracenteses in the month before screening. Has had a bowel obstruction within the last 3 months or is high risk for bowel obstruction or has a current need for parenteral nutrition. Has history of other illnesses in MUC16-expressing organs that could confuse the evaluation of DLTs due to including clinically significant uveitis, keratitis, or pancreatitis within the last 5 years Has uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B (HBV) or hepatitis C (HCV) infection; or diagnosis of immunodeficiency. NOTES: Patients with known HIV infection who have controlled infection (undetectable viral load [HIV RNA PCR] and CD4 count above 350 either spontaneously or on a stable antiviral regimen) are permitted. For patients with controlled HIV infection, monitoring will be performed per local standards. Surface antigen positive (HepBsAg+) who have controlled infection (serum hepatitis B virus DNA PCR that is below the limit of detection AND receiving antiviral therapy for hepatitis B) are permitted. Participants with HBsAg negative but total HBV core antibody positive (HBc Ab+) are permitted with the following requirements: If serum HBV DNA PCR is above the limit of detection at screening, antiviral therapy for HBV must be initiated prior to study entry. If serum HBV DNA PCR is below the limit of detection periodic monitoring of HBsAg must be performed. Patients who are hepatitis C virus antibody positive (HCV Ab+) who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) may be enrolled into the study. Active infections including: • Infection requiring hospitalization or treatment with IV anti-infectives within 2 weeks of start of study therapy • Known active tuberculosis or history of incompletely treated active or latent tuberculosis. Acceptable treatments for latent tuberculosis would be 9 months of isoniazid 300 mg by mouth daily or equivalent proven regimen per local guidelines. (For patients who are to receive sarilumab, exclusion of tuberculosis with an interferon gamma release assay is required unless there is a prior history of treated tuberculosis) • History of invasive opportunistic infections including but not limited to histoplasmosis, coccidioidomycosis, Pneumocystis jirovecii, or aspergillosis, or John Cunningham virus (progressive multifocal leukoencephalopathy) Has received a live vaccine within 4 weeks of planned start of study drug. Has received a COVID-19 vaccination within 1 week of planned start of study medication or for which the planned COVID-19 vaccinations would not be completed 1 week prior to start of study drug. Has had prior allogeneic stem cell transplantation or recipients of organ transplants at any time, or autologous stem cell transplantation within 12 weeks of the start of study drug. Has known psychiatric or substance abuse disorders that would interfere with participation with the requirements of the study. 30. Has any medical condition, co-morbidity, physical examination finding, or metabolic dysfunction, or clinical laboratory abnormality that, in the opinion of the investigator, renders the patient unsuitable for participation in a clinical trial due to high safety risks and/or potential to affect interpretation of results of the study 31. Severe and/or uncontrolled hypertension at screening. Patients taking anti-hypertensive medication must be on a stable anti-hypertensive regimen. 32. Has known allergy or hypersensitivity to cemiplimab and/or components of study drug(s). [0176] Study Treatments [0177] Module 1 – mAb1 (0.1 mg up to 300 mg) will be administered by once weekly intravenous (IV) infusion over up to 2 hours. After a minimum of a 3-week monotherapy lead-in of mAb1, cemiplimab 350 mg will be administered concomitantly every 3 weeks (Q3W) by IV infusion over 30 minutes. When both drugs are administered on the same day, cemiplimab will be administered first. [0178] Module 2 – mAb2 will be administered once weekly by IV infusion for up to 4 hours. After a 4-week monotherapy lead-in of mAb2, mAb1 (0.03 mg up to 30 mg) will be administered by once weekly IV infusion over up to 2 hours. When both drugs are administered on the same day, mAb1 will be administered first. [0179] A single dose of sarilumab (350 mg IV) over 60 minutes may be given prior to the first dose of REGN4018 for CRS prophylaxis. [0180] Study Endpoints [0181] The primary endpoints in the dose escalation phase are: • Dose-limiting toxicities (DLTs) • Treatment-emergent adverse events (TEAEs) • Serious adverse events (SAEs) • Deaths • Laboratory abnormalities (Grade 3 or higher per National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] version 5.0 [v5.0]) • Concentrations of mAb1 in serum when dosed alone and in combinations with cemiplimab or mAb2 [0182] The primary endpoint in the dose expansion phase is objective response rate (ORR) defined by RECIST 1.1 in combination with cemiplimab or mAb2 (separately by cohort and combination) [0183] The secondary endpoint in the dose escalation phase is ORR based on RECIST 1.1. [0184] The secondary endpoints in the dose expansion phase are: TEAEs, SAEs, deaths, and laboratory abnormalities (grade 3 or higher per NCI-CTCAE v5.0); and concentration of mAb1, mAb2, and cemiplimab in serum over time. [0185] The secondary endpoints in both the dose escalation and dose expansion phases are: ORR based on iRECIST, BOR, DOR, DCR, PFS based on RECIST 1.1 and iRECIST; cancer antigen 125 (CA-125) change from baseline after treatment with mAb1 in combinations with cemiplimab or mAb2 (separately by cohort and combination); and presence or absence of anti-drug antibodies against mAb1, mAb2 and cemiplimab. [0186] Primary Efficacy Analysis - the objective response rate (ORR) will be summarized by descriptive statistics, along with 95% confidence interval. Patients who are not evaluable for the ORR will be considered as non-responders. For the expansion cohorts, if the number of responders is greater than or equal to the minimum number of responders specified in the Simon 2-stage design, the treatment is considered as effective and worthy of further investigation. The statistical analyses of efficacy for each expansion cohort will be conducted and reported separately, i.e., efficacy results and clinical conclusions from each cohort will not affect the other cohort, and vice versa. [0187] Secondary Efficacy Analysis - surrogates of efficacy, such as best overall response (BOR) and disease control rate (DCR), and correlated biomarkers such as changes in CA-125 levels will be summarized by descriptive statistics, along with 95% confidence interval. Duration of response (DOR) and progression-free survival (PFS) will be summarized by median and its 95% confidence interval using the Kaplan-Meier method. [0188] Safety Analysis – safety observations and measurements including drug exposure, AEs, laboratory data, and vital signs will be summarized and presented in tables and listings. Particularly for the dose escalation phase: DLTs observed during DLT evaluation period will be summarized by dose cohort. [0189] Preliminary Results – 28 patients were enrolled. All patients received ≥1 of REGN5668 and 22 patients (79%) received ≥1 dose of cemiplimab. Median age was 58 years and 75% of patients had high-grade serous histology (Table 6). Patients had high-risk features: Median number of years since diagnosis was 2.8 (range 0.8-15.6); Median number of prior therapies was 3.5 (range 1−10); percentage of patients with prior bevacizumab (79%), PARP inhibitors (46%), immune checkpoint inhibitor (21%), and antibody-drug conjugate (11%). Median duration of REGN5668 and cemiplimab exposure was 7.5 (range 1.9-39.0) and 6.1 (2.4−36.0) weeks, respectively. Across all patients treated to date, one confirmed partial response (-59% target lesion reduction from baseline) and one CA-125 response were observed, both in a single patient at 300 mg. Six (21%) patients had stable disease. There was a dose-dependent increase in REGN5668 exposure between 1 mg and 300 mg IV QW dosing. Multiplex cytokine profiling (19 total cytokines, including IFNγ, IP-10, IL-6) using V-Plex Pro-inflammatory Panel 1 and Chemokine Panel 1 was exploratory. Cytokine analyses revealed no apparent elevations after REGN5668 dosing, while upon cemiplimab addition, slight increases in IFNγ and IP10 were observed. Collectively, these cytokine profiles were less pronounced than with CD3 bispecific antibodies and in line with lower rates of clinically evident CRS observed in this study. Overall, 24 (86%) of patients experienced ≥1 treatment related adverse event (TRAE) (Table 7), with fatigue (32%), nausea (29%) and pain (18%) being the most common TRAEs. Infusion related reactions (IRR) occurred in 2 (7%) patients (Grade 2 events), and cytokine release syndrome (CRS) occurred in 3 (11%) patients (two Grade 1 and one Grade 2 events). One (4%) Grade 3 TRAE (fatigue) occurred. Immune-mediated adverse reactions were observed in 2 (7%) patients, but there were no adverse events resulting in death or study drug discontinuation. No dose-limiting toxicities have been observed up to 1000 mg. Table 6: Demographics and Baseline Clinical Characteristics Variable Total (N=28) A

25; ECOG, Eastern Cooperative Oncology Group; IQR, interquartile range; U, units. Table 7: Safety Summary over the Entire Treatment Period Total (N=28) All grades Grade 3^§ ed term

values may be greater than the total of the higher-level category value. ^†One Grade 2 CRS after the first dose of cemiplimab; one Grade 1 CRS after the second dose of cemiplimab; one Grade 1 CRS after the first dose of REGN5668 confounded by concurrent infections. One Grade 2 IRR attributed to cemiplimab; one Grade 2 IRR attributed to REGN5668. ^§There were no Grade 4 or 5 TRAEs. CRS, cytokine release syndrome; IRR, infusion-related reaction; TRAE, treatment-related adverse event. [0190] Conclusion – In recurrent platinum-experienced ovarian cancer patients, an acceptable safety profile, low rates of CRS, and early activity were observed with REGN5668 + cemiplimab treatment. Example 4: A Phase 1/2 Study of a Bispecific Anti-MUC16 x Anti-CD28 Antibody Administered in Combination with an Anti-PD-1 Antibody or a Bispecific Anti-MUC16 x Anti- CD3 Antibody in Patients with Recurrent Advanced Endometrial Cancer [0191] This is a phase 1/2, first-in-human, open-label, multicenter, dose-escalation study with cohort expansion of the safety, tolerability, efficacy, and pharmacokinetics of mAb1, a MUC16 x CD28 bispecific antibody, administered with a monotherapy lead-in, in combination with the PD-1 antibody cemiplimab (Module 1) and, separately, in combination with the MUC16 x CD3 bispecific antibody mAb2 (Module 2) in patients with recurrent advanced endometrial cancer (after 1 to 2 prior lines of therapy including anti-PD-1 therapy and prior platinum-based chemotherapy administered together or separately). The patient population includes patients with recurrent advanced endometrial cancer with >25% of tumor cells MUC16 positive by immunohistochemistry (IHC) after prior anti-PD-1 and prior platinum-based therapy. [0192] Study Objectives [0193] The primary objectives of the study are: (i) to assess the safety, tolerability, and pharmacokinetics (PK) of mAb1 (REGN5668) alone and in separate combinations with cemiplimab or mAb2 (REGN4018), in order to determine a maximally tolerated dose(s) (MTD) or recommended phase 2 dose(s) (RP2D) of mAb1 in these combinations (in the dose escalation phase); and (ii) to assess the preliminary efficacy of mAb1 in combination with cemiplimab or mAb2, (separately by cohort and combination) as determined by the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (in the dose expansion phase). [0194] The secondary objectives of the study are: (i) to assess the preliminary efficacy of mAb1 in combination with cemiplimab or mAb2 (separately by cohort and combination) as determined by objective response rate (ORR) by RECIST 1.1 (in the dose escalation phase); (ii) to characterize the safety profile in each expansion cohort (in the dose expansion phase); (iii) to characterize the PK of mAb1 in combination with cemiplimab or mAb2 (separately by cohort and combination) (in the dose expansion phase); (iv) to assess preliminary efficacy of mAb1 in combination with cemiplimab or mAb2 (separately by cohort and combination) as measured by ORR based on immune based therapy RECIST (iRECIST), best overall response (BOR), duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS) based on RECIST 1.1 and iRECIST (in both the dose escalation and dose expansion phases); (v) to assess changes in CA-125 level from baseline after treatment with mAb1 in combinations with cemiplimab or mAb2 (separately by cohort and combination) (in both the dose escalation and dose expansion phases); and (vi) immunogenicity of mAb1, alone and in combinations with cemiplimab or mAb2 (in both the dose escalation and dose expansion phases). [0195] The exploratory objectives of the study are: • To evaluate biomarkers that may correlate with mechanism of action, increase understanding of disease/on-target activity, observed toxicity, and potential anti-tumor activity, or markers that may be predictors of efficacy and/or safety, which may include but are not limited to: • MUC16 and programmed cell death-ligand 1 (PD-L1) expression in tumors • Intratumoral and circulating immune cell populations • Plasma cytokines, chemokines and other circulating proteins • Intratumoral gene/transcript expression, tumor and circulating gene mutational burden • Where possible, to evaluate the relationship between exposure and efficacy, biomarker and safety endpoints • To assess overall survival (OS) [0196] Study Design [0197] This is a phase 1/2 dose-escalation study with cohort expansion of the safety, tolerability, efficacy, and pharmacokinetics of mAb1, REGN5668, a MUC16xCD28 bispecific antibody, administered with a monotherapy lead-in, in combination with the PD-1 antibody cemiplimab (Module 1) and, separately, in combination with the MUC16xCD3 bispecific antibody, REGN4018, mAb2 (Module 2) in patients with recurrent advanced endometrial cancer. The patient population includes patients with recurrent advanced endometrial cancer with >25% of tumor cells MUC16 positive by IHC after prior anti-PD-1 and prior platinum-based therapy. The study contains separate dose escalation modules and separate dose expansion cohorts for each combination. Each module contains a series of dose escalation cohorts. Modules will have a staggered start beginning with Module 1. [0198] Module 1: mAb1 in combination with cemiplimab - during dose escalation, patients will receive a 3- to 4-week monotherapy lead-in of mAb1 (cycle 0) at the assigned dose level (DL) intravenously (IV) weekly (QW), followed by combination therapy of mAb1 at the assigned DL IV QW and cemiplimab 350 mg IV once every three weeks (Q3W) (cycle 1 and beyond). [0199] Combination therapy with cemiplimab will begin on cycle 1 day 1 after completion of a mAb1 monotherapy lead-in cycle (cycle 0). Cycle 1 will be initiated only after the patient has 1) received at least 3 doses of mAb1, and 2) does not develop cytokine release syndrome (CRS) in the last mAb1 infusion of cycle 0 according to updated ASTCT criteria and after sponsor review of safety data. The starting date of cycle 1 day 1 will be no earlier than 21 days from cycle 0 day 1 and no later than 28 days from cycle 0 day 1. Thus, the length of cycle 0 may differ between patients but will be no more than 4 weeks. [0200] Treatment for each patient will continue as established in cycle 1 for the respective dose level until disease progression or intolerable toxicity occurs. [0201] The purpose of the dose escalation cohorts in Module 1 is to evaluate mAb1 monotherapy and identify an MTD or RP2D of mAb1 for testing in combination with cemiplimab (in the Module 1 dose expansion cohort). The dose-limiting toxicity (DLT) period for determining safety for dose escalation in Module 1 is defined as 42 days (or up to 49 days if initiation of combination therapy is delayed) starting with cycle 0 day 1. The intent of the DLT observation period in Module 1 is to monitor the safety and tolerability of at least the first 3 doses of mAb1 in monotherapy and the first 3 weeks of combination therapy with cemiplimab. [0202] Additional cohorts may assess whether the mAb1 monotherapy lead-in may be shortened or removed prior to Module 1 expansion. [0203] The primary purpose of the Module 1 dose expansion cohort will be to assess the preliminary efficacy of the mAb1 RP2D in combination with cemiplimab, using a Simon’s 2-stage design. Dose escalation will proceed as shown in Table 8. Table 8: Dose Escalation for Module 1 (mAb1 and cemiplimab) Dose Level mAb1 Cemiplimab M1-DL-1* 01 m 350 m

g p g . [0204] Module 2: mAb1 in combination with mAb2 - module 2 will begin after at least 2 dose levels in Module 1 have been tolerated. [0205] Patients will receive 4 to 5-weeks of monotherapy of mAb2 IV QW (cycle 0; including initial, transitional, and at least 2 full doses) followed by combination therapy of mAb1 with full dose mAb2. For each patient, combination therapy will begin after the monotherapy lead-in of mAb2 is well tolerated (i.e., no CRS per updated ASTCT criteria in the last mAb2 monotherapy dose given). The DLT period in Module 2 is defined as 21 days (or up to 28 days if the administration of full dose mAb1 is delayed) after the start of mAb1 administration (beginning on cycle 1 day 1) (i.e., it will not include the mAb2 monotherapy lead-in [cycle 0]). The intent of the DLT observation period for dose escalation in Module 2 is to monitor the safety and tolerability of the first 3 weeks of the combination of mAb2 and mAb1. [0206] The primary purpose of the Module 2 dose expansion cohort (described in greater detail below) will be to assess the preliminary efficacy of the mAb1 RP2D in combination with mAb2, using a Simon’s 2-stage design. Dose escalation will proceed as shown in Table 9. Table 9: Dose Escalation for Module 2 (mAb1 and mAb2) Dose Level mAb2 mAb2 mAb2 mAb1 mAb1 Initial Dose Transitional Dose** Full Dose Initial Dose Full Dose

[0207] Assessment of Dose Limiting Toxicities in Dose Escalation - at least 3 patients will initially be enrolled at each DL (except for the first DL in Modules 1 and 2). The following rules will be used to assign a DL to the next group of patients: • If the number of patients who experience a DLT at the current DL is less than or equal to the escalation boundary specified, dose will be escalated to the next higher DL. If DLT rates in the first group of patients allow for dose escalation, additional DLT-evaluable patients may be added to the current DL before a decision is made to escalate the dose in order to further evaluate safety. • If the number of patients who experience a DLT at the current DL is greater than or equal to the de-escalation boundary but less than elimination boundary, dose will be de-escalated to the next lower DL. • If the number of patients who experience a DLT at the current DL is greater than or equal to the elimination boundary, the current and all higher DLs will be eliminated from the trial to prevent treating any further patients at these doses. When a dose is eliminated, the dose will be de-escalated to the next lower DL for subsequent subjects. • If none of the actions (i.e., escalation, de-escalation or elimination) are triggered, additional patients may be treated at the current DL. • If the accumulated number of patients treated at the current DL reaches 12, escalation may be stopped to select the MTD/ presumptive RP2D per clinical judgment. [0208] The DLT criteria take into consideration 1) Which normal tissues have MUC16 expression, 2) toxicology findings in cynomolgus monkeys treated with monotherapy cemiplimab, mAb1 or mAb2, mAb1 in combination with mAb2, and mAb1 in combination with cemiplimab and mAb2, 3) adverse events in patients treated with mAb2 and/or with cemiplimab in clinical studies or post- marketing use, and 4) experiences with other bispecific and costimulatory antibodies in humans. The same DLT criteria are used in both modules, although the timing and duration of the DLT period differ and are based on the sequencing of study drugs in each module. [0209] During dose escalation, additional data may be collected on safety, efficacy, and other biological information to better inform expansion dose selection. To collect such data, up to 6 additional patients may be enrolled in up to 2 dose levels per module. While adverse events observed in these patients will be considered in dose escalation decisions, these additional patients will not formally be part of the algorithm for determining the MTD. [0210] Dose Expansion for Module 1 and Module 2 - after identification of the mAb1 MTD/RP2Ds of a combination regimen, 50-patient expansion cohorts will be opened for that combination regimen using a Simon 2-stage design (n=20 patients in stage 1; n=30 patients in stage 2). The enrollment of stage 2 for each expansion cohort will occur only if the minimum number of tumor responses is observed at stage 1. Dose levels of mAb1 may differ between Module 1 and 2 expansion cohorts. [0211] If a patient develops grade ≥2 CRS at any DL of mAb1, a strategy of utilizing premedications and possibly a transitional dose between the initial and full doses will be used in subsequent patients in the same DL and subsequent DLs per the following guidance: • Module 1 only: In the case of grade ≥2 CRS with the initial or subsequent doses, premedication with antihistamines and acetaminophen (and optionally corticosteroids) may be used for subsequent patients enrolled at that DL. • Module 1 only: If dosing is tolerated during the monotherapy lead-in cycle, but grade ≥2 CRS is first observed upon combination with cemiplimab and persists in the setting of premedication, then the first dose of mAb1 given in combination with cemiplimab (i.e., cycle 1 day 1) may be limited to the highest dose of mAb1 administered in combination with cemiplimab without the development of CRS. For patients in higher DL cohorts, a transitional dose that is considered to be tolerable at the time may be administered before administering the full dose for the DL. Example: if during the monotherapy lead-in for Module 1 at DL3, 3 mg is administered without CRS, but 3 mg administered in combination with cemiplimab in cycle 1 day 1 is associated with grade ≥2 CRS, then subsequent patients at DL3 will be administered 1 mg on cycle 1 day 1 for their first combination dose with cemiplimab, and the following doses will be administered at 3 mg. • Module 2 only: Premedication with antihistamines and acetaminophen (and optionally corticosteroids) is required. If grade ≥2 CRS persists in the setting of premedication with the initial dose at any DL in Module 2, then the initial mAb1 dose for subsequent study patients may be limited to the highest dose administered without the development of more than mild/moderate IRR/CRS. Example: if DL4 (0.3 mg) is associated with severe IRR/CRS at cycle 1 day 1, but DL3 (0.1 mg dose) was tolerated without more than mild/moderate CRS, the subsequent patients in DL4 and subsequent DLs may receive 0.1 mg for the initial dose followed by 0.3 mg for the subsequent dose. Subsequent cohorts may also receive 0.1 mg for the initial dose, even as the DL continues to escalate. For patients in higher DL cohorts, a transitional dose of mAb1 that is considered to be tolerable at the time may be administered before administering the full dose of mAb1 for the DL. [0212] Study Duration [0213] The total duration of study participation for each patient will vary based on the occurrence of 1 or more of the following: disease progression, intolerable AEs, withdrawal of consent, or study withdrawal criterion is met. The study will consist of 4 periods, including: • Screening period (up to 28 days) • Monotherapy lead-in − Module 1: mAb1 lead-in 3 to 4 weeks (21 to 28 days) − Module 2: mAb2 lead-in 4 to 5 weeks (28 to 35 days) • Combination therapy treatment period (variable duration) • Follow-up period (approximately 90 days from last dose for patients who discontinue due to disease progression or toxicity, or who start another therapy; approximately 168 days from last dose for patients who discontinue in the setting of complete response) [0214] Study Population [0215] A maximum of 412 patients will be enrolled for the study (up to 212 patients in the dose escalation phase, and up to 200 patients in the dose expansion phase). [0216] The study population includes patients with recurrent advanced endometrial cancer with >25% of tumor cells MUC16 positive by immunohistochemistry (IHC) after prior anti-PD-1 and prior platinum-based therapy. [0217] Inclusion Criteria: A patient must meet the following criteria to be eligible for inclusion in the study: 1. Is a woman ≥18 years of age. 2. Histologically confirmed endometrial cancer that has progressed or is recurrent after prior PD-1 therapy and platinum-based chemotherapy. a. MUC16-positivity of ≥25% of tumor cells by a validated MUC16 Immunohistochemistry b. Prior treatment with anti-PD(L)-1 therapy and prior platinum-based chemotherapy c. 1 to 2 prior lines of systemic chemotherapy, does not include systemic adjuvant therapy administered >12 months before 1^st treatment in the recurrent setting or hormonal therapy as a line 3. Patients must provide either newly obtained biopsy (newly obtained biopsies at screening are required unless medically inappropriate and discussed with medical monitor). If fresh biopsies are not appropriate, and after sponsor approval, archived tumor tissue in dose escalation is acceptable. In dose expansion, patients will provide a fresh tumor biopsy in screening and on treatment. Hence, in expansion cohorts, only patients who (in the opinion of the investigator) have accessible lesions that can be biopsied without significant risk to the patient are eligible. 4. Expansion cohorts only: Has at least 1 lesion that is measurable by RECIST 1.1. Tumor lesions in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions after radiation. 5. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 6. Has adequate organ and bone marrow function documented by: a. Hemoglobin ≥8.5 g/dL. b. Absolute neutrophil count ≥1.5x 10⁹/L. c. Platelet count ≥75 x 10⁹/L. d. Serum creatinine ≤1.5 x ULN or estimated glomerular filtration rate >50 mL/min/1.73m² (according to MDRD or CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation). A 24-hour urine creatinine collection may substitute for the calculated creatinine clearance to meet eligibility criteria. e. Adequate hepatic function: a. Total bilirubin ≤1.5 x ULN (≤3 x ULN if tumor liver involvement or known Gilbert’s Syndrome) b. Aspartate Aminotransferase (AST) ≤2.5 x ULN (≤5 x ULN if tumor liver involvement) c. Alanine Aminotransferase (ALT) ≤2.5 x ULN (≤5 x ULN if tumor liver involvement) d. Alkaline Phosphatase (ALP) ≤2.5 x ULN (≤5 x ULN if tumor liver or bone involvement) NOTES: In patients with tumor liver involvement if levels of AST ≥3 x ULN or ALT ≥3 x ULN, and bilirubin levels ≥2 x ULN will be excluded regardless of the above criteria. 7. Has a life expectancy of at least 3 months. 8. Is willing and able to comply with clinic visits and study-related procedures and requirements. 9. Is willing and able to provide informed consent as specified by health authorities and institutional guidelines. 10. Can understand and complete study-related questionnaires, if applicable. [0218] Exclusion Criteria: A patient who meets any of the following criteria will be excluded from the study: 1. Is currently receiving treatment in another study. 2. Within 60 days (approximately 3 half-lives) since last administration of anti-PD-1 therapy. 3. Has received treatment with an approved systemic therapy (except biologics and/or immunotherapy) within 3 weeks or has not yet recovered (i.e., grade ≤ 1 or baseline) from any acute toxicities except for chronic grade ≤2 neuropathy, chronic hearing loss, or laboratory changes as described in inclusion criteria. 4. Has received any previous systemic biologic therapy within 5 half-lives of first dose of study drug or 28 days, whichever is longer, except as follows: Patients previously treated with cetuximab, rituximab, or other non-immunomodulatory antibodies with half-lives longer than 7 days are permitted after a discussion with the sponsor if at least 3 half-lives have elapsed since last treatment. Note: Patients previously treated with bevacizumab are permitted if there was no history of bowel perforation or wound complications on bevacizumab AND the last dose was >30 days from the first dose of REGN5668 (in Module 1) or REGN4018 (in Module 2). 5. Prior anti-cancer immunotherapy as described below: • Recent anti-PD-1/PD-L1 therapy (within 60 days ~3 half-lives since last dose of therapy) • Received CAR-T within 30 days of first dose of study drug • Has not recovered (i.e., grade ≤1 or baseline) from immune-mediated adverse events of grade 2 or higher at least 1 month prior to initiation of study drug are excluded. Endocrinopathies adequately managed with hormone replacement and vitiligo are not exclusionary Has received radiation therapy or major surgery within 14 days of first administration of study drug or has not recovered (i.e., grade ≤1 or baseline) from adverse events, except for chronic grade ≤2 neuropathy or laboratory changes as described in inclusion criteria. Has had another malignancy within the last 5 years that is progressing, requires active treatment, or has a high likelihood of recurrence. Exceptions include: • Non-melanoma skin cancer that has undergone potentially curative therapy • In situ cervical carcinoma • Any tumor that has been deemed to be effectively treated with definitive local control (with or without continued adjuvant hormonal therapy). Prior treatment with a MUC16-targeted therapy. Expansion cohorts only: More than 4 prior lines of cytotoxic chemotherapy (including antibody drug conjugates). Note: In dose-escalation cohorts there is no maximum limit on prior lines of therapy. Has any condition that requires ongoing/continuous corticosteroid therapy (>10 mg prednisone/day or anti-inflammatory equivalent) within 1 week prior to the first dose of study drug. Physiologic replacement doses are allowed even if they are >10 mg of prednisone/day or equivalent, provided they are not being administered for immunosuppressive intent. Inhaled, intranasal, or topical steroids are permitted, provided that they are not for treatment of an autoimmune disorder. Note: Patients who require a brief course of steroids (up to 2 days in the week before enrollment) may be enrolled in the study. Has ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments. The following are not exclusionary: vitiligo, childhood asthma that has resolved, endocrinopathies (such as hypothyroidism or type 1 diabetes) that require only hormone replacement, or psoriasis that does not require systemic treatment. Has untreated or active primary brain tumor, CNS metastases, leptomeningeal disease, or spinal cord compression. Exception: Patients with previously treated central nervous system metastases or spinal cord compression may participate provided: • No evidence of progression for at least 4 weeks prior to the first dose of study drug, and any neurologic symptoms have returned to baseline • No evidence of new or enlarging central nervous system metastases • No requirement for systemic corticosteroids for management of central nervous system metastases or spinal cord compression within 2 weeks prior to the first dose of study drug Has encephalitis, meningitis, organic brain disease (e.g., Parkinson’s disease) or uncontrolled seizures in the year prior to first dose of study drug. Has a clinically significant abnormal ECG reading, and/or the following criteria: • QTc [Fredericia] interval>470 msec − In cases of asymptomatic prolonged QTc interval (>470 msec), the ECG can be repeated up to 2 times. If subsequent QTc interval is <470 msec, the patient may be enrolled only after review and approval by a cardiologist. • Evidence of Second-Degree AV block type II (Mobitz type II) or AV block type III (complete heart block) • Has a history of any clinically significant arrhythmia including atrial fibrillation or implantation of a pacemaker or defibrillator Has any history of the following: • Myocarditis • Clinically significant valvular heart disease (generally moderate or greater in severity), uncorrected with surgical or transcatheter valve procedure Has history of clinically significant cardiovascular disease including but not limited to the following, within 6 months prior to screening: • Myocardial infarction • Unstable angina • Stroke or transient ischemic attack • Peripheral arterial disease event • Heart failure (NYHA class III and IV or ACC/AHA heart failure classification C or D) • Signs or symptoms of active angina or heart failure, including left ventricular ejection fraction (LVEF) less than 50% as measured by echocardiogram at baseline. In cases of LVEF 45-50% in absence of clinical symptoms, after review and clearance by a cardiologist, the patient may be enrolled. Has moderate to large pericardial effusion (e.g., >approximately 100 mL) as measured by echocardiogram at baseline. Baseline serum troponin above institutional upper limit of normal. In cases of minimally elevated troponin in absence of clinical symptoms, and after clearance by a cardiologist, the patient may be enrolled. Has a known history of, or any evidence of, interstitial lung disease or active, non-infectious pneumonitis within 5 years prior to the first dose of study drug. A history of radiation pneumonitis in a radiation field is permitted. Has moderate to large pleural effusion at baseline that may require thoracentesis within the next 4 weeks due to size or rate of enlargement. Pre-existing chest tube is acceptable, if patient meets all other inclusion/exclusion criteria. Requires 2 or more therapeutic paracenteses in the month before screening. Has had a bowel obstruction within the last 3 months or is high risk for bowel obstruction or has a current need for parenteral nutrition. Has history of other illnesses in MUC16-expressing organs that could confuse the evaluation of DLTs due to including clinically significant uveitis, keratitis, or pancreatitis within the last 5 years Has uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B (HBV) or hepatitis C (HCV) infection; or diagnosis of immunodeficiency. NOTES: Patients with known HIV infection who have controlled infection (undetectable viral load [HIV RNA PCR] and CD4 count above 350 either spontaneously or on a stable antiviral regimen) are permitted. For patients with controlled HIV infection, monitoring will be performed per local standards. Surface antigen positive (HepBsAg+) who have controlled infection (serum hepatitis B virus DNA PCR that is below the limit of detection AND receiving antiviral therapy for hepatitis B) are permitted. Participants with HBsAg negative but total HBV core antibody positive (HBc Ab+) are permitted with the following requirements: If serum HBV DNA PCR is above the limit of detection at screening, antiviral therapy for HBV must be initiated prior to study entry. If serum HBV DNA PCR is below the limit of detection periodic monitoring of HBsAg must be performed. Patients who are hepatitis C virus antibody positive (HCV Ab+) who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) may be enrolled into the study. 25. Active infections including: • 25.Infection requiring hospitalization or treatment with IV anti-infectives within 2 weeks of start of study therapy • Known active tuberculosis or history of incompletely treated active or latent tuberculosis. Acceptable treatments for latent tuberculosis would be 9 months of isoniazid 300 mg by mouth daily or equivalent proven regimen per local guidelines. (For patients who are to receive sarilumab, exclusion of tuberculosis with an interferon gamma release assay is required unless there is a prior history of treated tuberculosis) • History of invasive opportunistic infections including but not limited to histoplasmosis, coccidioidomycosis, Pneumocystis jirovecii, or aspergillosis, or John Cunningham virus (progressive multifocal leukoencephalopathy) 26. Has received a live vaccine within 4 weeks of planned start of study drug. 27. Has received a COVID-19 vaccination within 1 week of planned start of study medication or for which the planned COVID-19 vaccinations would not be completed 1 week prior to start of study drug. 28. Has had prior allogeneic stem cell transplantation or recipients of organ transplants at any time, or autologous stem cell transplantation within 12 weeks of the start of study drug. 29. Has known psychiatric or substance abuse disorders that would interfere with participation with the requirements of the study. 30. Has any medical condition, co-morbidity, physical examination finding, or metabolic dysfunction, or clinical laboratory abnormality that, in the opinion of the investigator, renders the patient unsuitable for participation in a clinical trial due to high safety risks and/or potential to affect interpretation of results of the study 31. Severe and/or uncontrolled hypertension at screening. Patients taking anti-hypertensive medication must be on a stable anti-hypertensive regimen. 32. Has known allergy or hypersensitivity to cemiplimab and/or components of study drug(s). [0219] Study Treatments [0220] Module 1 – mAb1 (0.1 mg up to 300 mg) will be administered by once weekly intravenous (IV) infusion over up to 2 hours. After a minimum of a 3-week monotherapy lead-in of mAb1, cemiplimab 350 mg will be administered concomitantly every 3 weeks (Q3W) by IV infusion over 30 minutes. When both drugs are administered on the same day, cemiplimab will be administered first. [0221] Module 2 – mAb2 will be administered once weekly by IV infusion for up to 4 hours. After a 4-week monotherapy lead-in of mAb2, mAb1 (0.03 mg up to 30 mg) will be administered by once weekly IV infusion over up to 2 hours. When both drugs are administered on the same day, mAb1 will be administered first. [0222] A single dose of sarilumab (350 mg IV) over 60 minutes may be given prior to the first dose of REGN4018 for CRS prophylaxis. [0223] Study Endpoints [0224] The primary endpoints in the dose escalation phase are: • Dose-limiting toxicities (DLTs) • Treatment-emergent adverse events (TEAEs) • Serious adverse events (SAEs) • Deaths • Laboratory abnormalities (Grade 3 or higher per National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] version 5.0 [v5.0]) • Concentrations of mAb1 in serum when dosed alone and in combinations with cemiplimab or mAb2 [0225] The primary endpoint in the dose expansion phase is objective response rate (ORR) defined by RECIST 1.1 in combination with cemiplimab or mAb2 (separately by cohort and combination) [0226] The secondary endpoint in the dose escalation phase is ORR based on RECIST 1.1. [0227] The secondary endpoints in the dose expansion phase are: TEAEs, SAEs, deaths, and laboratory abnormalities (grade 3 or higher per NCI-CTCAE v5.0); and concentration of mAb1, mAb2, and cemiplimab in serum over time. [0228] The secondary endpoints in both the dose escalation and dose expansion phases are: ORR based on iRECIST, BOR, DOR, DCR, PFS based on RECIST 1.1 and iRECIST; cancer antigen 125 (CA-125) change from baseline after treatment with mAb1 in combinations with cemiplimab or mAb2 (separately by cohort and combination); and presence or absence of anti-drug antibodies against mAb1, mAb2 and cemiplimab. [0229] Primary Efficacy Analysis - the objective response rate (ORR) will be summarized by descriptive statistics, along with 95% confidence interval. Patients who are not evaluable for the ORR will be considered as non-responders. For the expansion cohorts, if the number of responders is greater than or equal to the minimum number of responders specified in the Simon 2-stage design, the treatment is considered as effective and worthy of further investigation. The statistical analyses of efficacy for each expansion cohort will be conducted and reported separately, i.e., efficacy results and clinical conclusions from each cohort will not affect the other cohort, and vice versa. [0230] Secondary Efficacy Analysis - surrogates of efficacy, such as best overall response (BOR) and disease control rate (DCR), and correlated biomarkers such as changes in CA-125 levels will be summarized by descriptive statistics, along with 95% confidence interval. Duration of response (DOR) and progression-free survival (PFS) will be summarized by median and its 95% confidence interval using the Kaplan-Meier method. [0231] Safety Analysis – safety observations and measurements including drug exposure, AEs, laboratory data, and vital signs will be summarized and presented in tables and listings. Particularly for the dose escalation phase: DLTs observed during DLT evaluation period will be summarized by dose cohort. [0232] Preliminary Results – patients in the dose escalation phase were administered REGN4018 in a step-up dosing regimen followed by 10 mg REGN5668. A single dose of phophylactic sarilumab was administered before REGN4018 to prevent or reduce CRS. Dose escalation continues. [0233] The present disclosure is not to be limited in scope by the specific embodiments described herein. Indeed, various modifications of the disclosure in addition to those described herein will become apparent to those skilled in the art from the foregoing description. Such modifications are intended to fall within the scope of the appended claims. Sequences SEQ ID NO: 1 EVQLVESGGGLEQPGRSLRLSCTASGFAFGDHTMSWVRQAPGKGLEWVGFIRSRAYGGTTEYAASVKGRF TISRDDSKSIAYLQMDSLKTEDTAVYYCTSGGYDSSLHYYYYYHGMDVWGRGTTVTVSS SEQ ID NO: 2 GFAFGDHT SEQ ID NO: 3 IRSRAYGGTT SEQ ID NO: 4 TSGGYDSSLHYYYYYHGMDV SEQ ID NO: 5 QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGITHYNPSLKSRVTISVDTS KIQFSLKLSSVTAADTAVYYCARWGVRRDYYYYGMDVWGQGTTVTVSS SEQ ID NO: 6 GGSISSYY SEQ ID NO: 7 IYYSGIT SEQ ID NO: 8 ARWGVRRDYYYYGMDV SEQ ID NO: 9 EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFT LTISRLEPEDFAVYYCQQYGSSPWTFGQGTKVEIK SEQ ID NO: 10 QSVSSSY SEQ ID NO: 11 GAS SEQ ID NO: 12 QQYGSSPWT SEQ ID NO: 13 EVQLVESGGGLEQPGRSLRLSCTASGFAFGDHTMSWVRQAPGKGLEWVGFIRSRAYGGTTEYAASVK GRFTISRDDSKSIAYLQMDSLKTEDTAVYYCTSGGYDSSLHYYYYYHGMDVWGRGTTVTVSSASTKGP SVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSS LGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSI EKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD GSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK SEQ ID NO: 14 QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGITHYNPSLKSRVTIS VDTSKIQFSLKLSSVTAADTAVYYCARWGVRRDYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPCSR STSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNV DHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQ FNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQ PREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLT VDKSRWQEGNVFSCSVMHEALHNRFTQKSLSLSPGK SEQ ID NO: 15 EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSG TDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNN FYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT KSFNRGEC SEQ ID NO: 16 QVQLVESGGGLVKPGGSLRLSCAASGFTFRDYSMSWIRQAPGKGLEWVSYVTFFNSAIYYADSVKGRFTISR DNAKNSLYLQMNSLRAEDTAVYYCAREREPIVGGFDYWGQGTLVTVSS SEQ ID NO: 17 GFTFRDYS SEQ ID NO: 18 VTFFNSAI SEQ ID NO: 19 AREREPIVGGFDY SEQ ID NO: 20 EVQLVESGGGLVQPGGSLRLSCAASGFTFSRNNMHWVRQAPGKGLEYVSGISSNGGRTYYADSVKGRFTIS RDNSKNTLYLQMGGLRAADMAVYFCTRDDELLSFDYWGQGTLVTVSS SEQ ID NO: 21 GFTFSRNN SEQ ID NO: 22 ISSNGGRT SEQ ID NO: 23 TRDDELLSFDY SEQ ID NO: 24 DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTL TISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK SEQ ID NO: 25 QSISSY SEQ ID NO: 26 AAS SEQ ID NO: 27 QQSYSTPPIT SEQ ID NO: 28 QVQLVESGGGLVKPGGSLRLSCAASGFTFRDYSMSWIRQAPGKGLEWVSYVTFFNSAIYYADSVKGRF TISRDNAKNSLYLQMNSLRAEDTAVYYCAREREPIVGGFDYWGQGTLVTVSSASTKGPSVFPLAPCSRS TSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVD HKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQF NWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQP REPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTV DKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK SEQ ID NO: 29 EVQLVESGGGLVQPGGSLRLSCAASGFTFSRNNMHWVRQAPGKGLEYVSGISSNGGRTYYADSVKGR FTISRDNSKNTLYLQMGGLRAADMAVYFCTRDDELLSFDYWGQGTLVTVSSASTKGPSVFPLAPCSRS TSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVD HKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQF NWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQP REPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTV DKSRWQEGNVFSCSVMHEALHNRFTQKSLSLSPGK SEQ ID NO: 30 DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGT DFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK SFNRGEC SEQ ID NO: 31 QVQLVESGGGLVKPGGSLRLSCAASGFTFSNYYMSWVRQAPGKGLEWISYISGRGSTIFYADSVKGRITISR DNAKNSLFLQMNSLRAEDTAVYFCVKDRGGYSPYWGQGTLVTVSS SEQ ID NO: 32 GFTFSNYY SEQ ID NO: 33 ISGRGSTI SEQ ID NO: 34 VKDRGGYSPY SEQ ID NO: 35 EVQLVESGGGLVQPGRSLRLSCAASGFTFDDYSMHWVRQAPGKGLEWVSGISWNSGSKGYADSVKGRFTI SRDNAKNSLYLQMNSLRAEDTALYYCAKYGSGYGKFYHYGLDVWGQGTTVTVSS SEQ ID NO: 36 GFTFDDYS SEQ ID NO: 37 ISWNSGSK SEQ ID NO: 38 AKYGSGYGKFYHYGLDV SEQ ID NO: 39 EVQLVESGGGLVQPGRSLRLSCAASGFTFDDYSMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTIS RDNAKNSLYLQMNSLRAEDTALYYCAKYGSGYGKFYYYGMDVWGQGTTVTVSS SEQ ID NO: 40 GFTFDDYS SEQ ID NO: 41 ISWNSGSI SEQ ID NO: 42 AKYGSGYGKFYYYGMDV SEQ ID NO: 43 DIQMTQSPSSLSASVGDRVTITCRASQSISTYLNWYQQKPGKAPKLLIYTASSLQSGVPSRFSGSGSGTDFTL TISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK SEQ ID NO: 44 QSISTY SEQ ID NO: 45 TAS SEQ ID NO: 46 QQSYSTPPIT SEQ ID NO: 47 QVQLVESGGGLVKPGGSLRLSCAASGFTFSNYYMSWVRQAPGKGLEWISYISGRGSTIFYADSVKGRITISR DNAKNSLFLQMNSLRAEDTAVYFCVKDRGGYSPYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALG CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRV ESKYGPPCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTK PREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALH NHYTQKSLSLSLGK SEQ ID NO: 48 EVQLVESGGGLVQPGRSLRLSCAASGFTFDDYSMHWVRQAPGKGLEWVSGISWNSGSKGYADSVKGRFTI SRDNAKNSLYLQMNSLRAEDTALYYCAKYGSGYGKFYHYGLDVWGQGTTVTVSSASTKGPSVFPLAPCSRS TSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKP SNTKVDKRVESKYGPPCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDG VEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPP SQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFS CSVMHEALHNRFTQKSLSLSPGK SEQ ID NO: 49 EVQLVESGGGLVQPGRSLRLSCAASGFTFDDYSMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTIS RDNAKNSLYLQMNSLRAEDTALYYCAKYGSGYGKFYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPCSRST SESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPS NTKVDKRVESKYGPPCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGV EVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPS QEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSC SVMHEALHNRFTQKSLSLSPGK SEQ ID NO: 50 DIQMTQSPSSLSASVGDRVTITCRASQSISTYLNWYQQKPGKAPKLLIYTASSLQSGVPSRFSGSGSGTDFTL TISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKV QWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC SEQ ID NO: 51 EVQLLESGGVLVQPGGSLRLSCAASGFTFSNFGMTWVRQAPGKGLEWVSGISGGGRDTYFADSVKGRFTIS RDNSKNTLYLQMNSLKGEDTAVYYCVKWGNIYFDYWGQGTLVTVSS SEQ ID NO: 52 GFTFSNFG SEQ ID NO: 53 ISGGGRDT SEQ ID NO: 54 VKWGNIYFDY SEQ ID NO: 55 DIQMTQSPSSLSASVGDSITITCRASLSINTFLNWYQQKPGKAPNLLIYAASSLHGGVPSRFSGSGSGTDFTLTI RTLQPEDFATYYCQQSSNTPFTFGPGTVVDFR SEQ ID NO: 56 LSINTF SEQ ID NO: 57 AAS SEQ ID NO: 58 QQSSNTPFT SEQ ID NO: 59 EVQLLESGGVLVQPGGSLRLSCAASGFTFSNFGMTWVRQAPGKGLEWVSGISGGGRDTYFADSVKGRFTIS RDNSKNTLYLQMNSLKGEDTAVYYCVKWGNIYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAAL GCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKR VESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKT KPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEAL HNHYTQKSLSLSLGK SEQ ID NO: 60 DIQMTQSPSSLSASVGDSITITCRASLSINTFLNWYQQKPGKAPNLLIYAASSLHGGVPSRFSGSGSGTDFTLTI RTLQPEDFATYYCQQSSNTPFTFGPGTVVDFRRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQ WKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC *******

Claims

What is claimed is: 1. A method of treating a MUC16-expressing cancer in a subject in need thereof, comprising administering to the subject a combination of a bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment thereof comprising a first antigen-binding domain that specifically binds mucin 16 (MUC16), and a second antigen-binding domain that specifically binds human CD28, and an anti-PD-1 antibody or antigen-binding fragment thereof that specifically binds programmed death 1 (PD-1) receptor, wherein the bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment thereof is administered to the subject at a dose of at least 0.1 mg.

2. The method of claim 1, wherein the anti-PD-1 antibody or antigen-binding fragment comprises: (a) three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) contained within a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 51; and (b) three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) contained within a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 55.

3. The method of claim 2, wherein the anti-PD-1 antibody or antigen-binding fragment comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 52, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 53, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 54.

4. The method of claim 2 or 3, wherein the anti-PD-1 antibody or antigen-binding fragment comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 56, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 57, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 58.

5. The method of any one of claims 2-4, wherein the anti-PD-1 antibody or antigen- binding fragment comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 51, and a LCVR comprising the amino acid sequence of SEQ ID NO: 55.

6. The method of claim 5, wherein the anti-PD-1 antibody or antigen-binding fragment is an anti-PD-1 antibody comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 59 and a light chain comprising the amino acid sequence of SEQ ID NO: 60.

7. The method of any one of claims 1-6, wherein the anti-PD-1 antibody or antigen- binding fragment is administered to the subject at a dose of from 300 to 400 mg once every three weeks.

8. The method of claim 7, wherein the anti-PD-1 antibody is administered to the subject at a dose of 350 mg once every three weeks.

9. The method of any one of claims 1-8, wherein the anti-PD-1 antibody is cemiplimab. 10. The method of any one of claims 1-9, wherein the bispecific anti-MUC16 x anti- CD28 antibody or antigen-binding fragment thereof is administered at a dose of 0.1 mg, 0.3 mg, 1 mg, 3 mg,

10 mg, 30 mg, 100 mg, 300 mg, or 1000 mg once weekly.

11. A method of treating a MUC16-expressing cancer in a subject in need thereof, comprising administering to the subject a combination of a bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment thereof comprising a first antigen-binding domain that specifically binds mucin 16 (MUC16), and a second antigen-binding domain that specifically binds human CD28, and a bispecific anti-MUC16 x anti-CD3 antibody or antigen-binding fragment thereof comprising a first antigen-binding domain that specifically binds mucin 16 (MUC16), and a second antigen-binding domain that specifically binds human CD3, wherein the bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment is administered to the subject at a dose of at least 0.03 mg.

12. The method of claim 11, wherein the first antigen-binding domain of the bispecific anti-MUC16 x anti-CD3 antibody or antigen-binding fragment comprises: (a) three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) contained within a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 31; and (b) three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) contained within a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 43.

13. The method of claim 12, wherein the first antigen-binding domain of the bispecific anti-MUC16 x anti-CD3 antibody or antigen-binding fragment comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 32, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 33, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 34.

14. The method of claim 12 or 13, wherein the first antigen-binding domain of the bispecific anti-MUC16 x anti-CD3 antibody or antigen-binding fragment comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 44, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 45, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 46.

15. The method of any one of claims 12-14, wherein the first antigen-binding domain of the bispecific anti-MUC16 x anti-CD3 antibody or antigen-binding fragment comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 31, and a LCVR comprising the amino acid sequence of SEQ ID NO: 43.

16. The method of any one of claims 12-15, wherein the second antigen-binding domain of the bispecific anti-MUC16 x anti-CD3 antibody or antigen-binding fragment comprises: (a) three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) contained within a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 35; and (b) three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) contained within a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 43.

17. The method of claim 16, wherein the second antigen-binding domain of the bispecific anti-MUC16 x anti-CD3 antibody or antigen-binding fragment comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 36, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 37, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 38.

18. The method of claim 16 or 17, wherein the second antigen-binding domain of the bispecific anti-MUC16 x anti-CD3 antibody or antigen-binding fragment comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 44, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 45, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 46.

19. The method of any one of claims 16-18, wherein the second antigen-binding domain of the bispecific anti-MUC16 x anti-CD3 antibody or antigen-binding fragment comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 35, and a LCVR comprising the amino acid sequence of SEQ ID NO: 43.

20. The method of any one of claims 12-15, wherein the second antigen-binding domain of the bispecific anti-MUC16 x anti-CD3 antibody or antigen-binding fragment comprises: (a) three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) contained within a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 39; and (b) three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) contained within a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 43.

21. The method of claim 20, wherein the second antigen-binding domain of the bispecific anti-MUC16 x anti-CD3 antibody or antigen-binding fragment comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 40, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 41, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 42.

22. The method of claim 20 or 21, wherein the second antigen-binding domain of the bispecific anti-MUC16 x anti-CD3 antibody or antigen-binding fragment comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 44, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 45, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 46.

23. The method of any one of claims 20-22, wherein the second antigen-binding domain of the bispecific anti-MUC16 x anti-CD3 antibody or antigen-binding fragment comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 39, and a LCVR comprising the amino acid sequence of SEQ ID NO: 43.

24. The method of any one of claims 12-23, wherein the bispecific anti-MUC16 x anti-CD3 antibody comprises a human IgG heavy chain constant region.

25. The method of claim 24, wherein the human IgG heavy chain constant region is isotype IgG1.

26. The method of claim 24, wherein the human IgG heavy chain constant region is isotype IgG4.

27. The method of claim 25 or 26, wherein the bispecific anti-MUC16 x anti-CD3 antibody comprises a chimeric hinge that reduces Fcɣ receptor binding relative to a wild-type hinge of the same isotype.

28. The method of any one of claims 24-27, wherein the first heavy chain or the second heavy chain of the bispecific anti-MUC16 x anti-CD3 antibody, but not both, comprises a CH3 domain comprising a H435R (EU numbering) modification and a Y436F (EU numbering) modification.

29. The method of any one of claims 11-23, wherein the bispecific anti-MUC16 x anti-CD3 antibody comprises a first heavy chain comprising the amino acid sequence of SEQ ID NO: 47.

30. The method of any one of claims 11-23, wherein the bispecific anti-MUC16 x anti-CD3 antibody comprises a second heavy chain comprising the amino acid sequence of SEQ ID NO: 48.

31. The method of any one of claims 11-23, wherein the bispecific anti-MUC16 x anti-CD3 antibody comprises a second heavy chain comprising the amino acid sequence of SEQ ID NO: 49.

32. The method of any one of claims 11-23, wherein the bispecific anti-MUC16 x anti-CD3 antibody comprises a first heavy chain comprising the amino acid sequence of SEQ ID NO: 47, a second heavy chain comprising the amino acid sequence of SEQ ID NO: 48, and a common light chain comprising the amino acid sequence of SEQ ID NO: 50.

33. The method of any one of claims 11-23, wherein the bispecific anti-MUC16 x anti-CD3 antibody comprises a first heavy chain comprising the amino acid sequence of SEQ ID NO: 47, a second heavy chain comprising the amino acid sequence of SEQ ID NO: 49, and a common light chain comprising the amino acid sequence of SEQ ID NO: 50.

34. The method of any one of claims 11-33, wherein the bispecific anti-MUC16 x anti-CD3 antibody is REGN4018.

35. The method of any one of claims 11-33, wherein the bispecific anti-MUC16 x anti-CD3 antibody is administered to the subject at a dose of from 0.01 mg to 1000 mg weekly.

36. The method of claim 35, wherein the bispecific anti-MUC16 x anti-CD3 antibody is administered to the subject at a dose of from 1 mg to 250 mg weekly.

37. The method of any one of claims 11-36, wherein the bispecific anti-MUC16 x anti-CD3 antibody or antigen-binding fragment is administered to the subject weekly for at least one week prior to administration of the bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment.

38. The method of claim 37, wherein the bispecific anti-MUC16 x anti-CD3 antibody or antigen-binding fragment is administered to the subject weekly for four weeks or at least four weeks prior to administration of the bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment.

39. The method of claim 37, wherein the bispecific anti-MUC16 x anti-CD3 antibody or antigen-binding fragment is administered to the subject weekly for five weeks or at least five weeks prior to administration of the bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment.

40. The method of any one of claims 11-39, wherein the bispecific anti-MUC16 x anti-CD3 antibody or antigen-binding fragment is administered weekly in a dosing regimen at a dose of 1 mg during week 1, at a dose of 20 mg during week 2, and at a dose of from 20 mg to 250 mg or 20 mg to 1000 mg during each subsequent week of the dosing regimen.

41. The method of any one of claims 11-40, wherein the bispecific anti-MUC16 x anti-CD3 antibody is administered to the subject as a split dose, optionally wherein the split dose is administered during week 1, or during week 1 and week 2, of a dosing regimen.

42. The method of claim 41, wherein the bispecific anti-MUC16 x anti-CD3 antibody is administered to the subject at a dose of 1 mg during week 1, at a dose of 20 mg during week 2, wherein the dose of 20 mg is split into two equal doses of 10 mg administered to the subject on two days during week 2, and at a dose of 250 mg or up to 1000 mg during each subsequent week of the dosing regimen.

43. The method of any one of claims 11-42, further comprising prophylactic administration of an anti-IL-6R antibody prior to administration of the bispecific anti-MUC16 x anti- CD3 antibody or antigen-binding fragment thereof.

44. The method of any one of claims 1-43, wherein the MUC16-expressing cancer is ovarian cancer, fallopian tube cancer, endometrial cancer or primary peritoneal cancer.

45. The method of any one of claims 1-44, wherein the MUC16-expressing cancer is resistant to platinum-based chemotherapy.

46. The method of any one of claims 1-44, wherein the subject has previously been treated with a platinum-based chemotherapy or an anti-PD-1 therapy.

47. The method of any one of claims 1-46, wherein the subject has a serum CA-125 level of greater than 70 U/ml.

48. The method of any one of claims 1-47, wherein the first antigen-binding domain of the bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises: (a) three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) contained within a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 1; and (b) three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) contained within a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 9.

49. The method of claim 48, wherein the first antigen-binding domain of the bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 2, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 3, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 4.

50. The method of claim 48 or 49, wherein the first antigen-binding domain of the bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 10, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 11, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 12.

51. The method of any one of claims 48-50, wherein the first antigen-binding domain of the bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 1, and a LCVR comprising the amino acid sequence of SEQ ID NO: 9.

52. The method of any one of claims 48-51, wherein the second antigen-binding domain of the bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises: (a) three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) contained within a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 5; and (b) three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) contained within a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 9.

53. The method of claim 52, wherein the second antigen-binding domain of the bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 6, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 8.

54. The method of claim 52 or 53, wherein the second antigen-binding domain of the bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 10, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 11, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 12.

55. The method of any one of claims 52-54, wherein the second antigen-binding domain of the bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 5, and a LCVR comprising the amino acid sequence of SEQ ID NO: 9.

56. The method of any one of claims 48-55, wherein the bispecific anti-MUC16 x anti-CD28 antibody comprises a human IgG heavy chain constant region.

57. The method of claim 56, wherein the human IgG heavy chain constant region is isotype IgG1.

58. The method of claim 56, wherein the human IgG heavy chain constant region is isotype IgG4.

59. The method of claim 57 or 58, wherein the bispecific anti-MUC16 x anti-CD28 antibody comprises a chimeric hinge that reduces Fcɣ receptor binding relative to a wild-type hinge of the same isotype.

60. The method of any one of claims 56-59, wherein the first heavy chain or the second heavy chain of the bispecific anti-MUC16 x anti-CD28 antibody, but not both, comprises a CH3 domain comprising a H435R (EU numbering) modification and a Y436F (EU numbering) modification.

61. The method of any one of claims 48-60, wherein the bispecific anti-MUC16 x anti-CD28 antibody comprises a first heavy chain comprising the amino acid sequence of SEQ ID NO: 13.

62. The method of any one of claims 48-60, wherein the bispecific anti-MUC16 x anti-CD28 antibody comprises a second heavy chain comprising the amino acid sequence of SEQ ID NO: 14.

63. The method of any one of claims 48-60, wherein the bispecific anti-MUC16 x anti-CD28 antibody comprises a first heavy chain comprising the amino acid sequence of SEQ ID NO: 13, a second heavy chain comprising the amino acid sequence of SEQ ID NO: 14, and a common light chain comprising the amino acid sequence of SEQ ID NO: 15.

64. The method of any one of claims 1-47, wherein the first antigen-binding domain of the bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises: (a) three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) contained within a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 16; and (b) three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) contained within a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 24.

65. The method of claim 64, wherein the first antigen-binding domain of the bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 18, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 19.

66. The method of claim 64 or 65, wherein the first antigen-binding domain of the bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 25, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 26, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 27.

67. The method of any one of claims 64-66, wherein the first antigen-binding domain of the bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 16, and a LCVR comprising the amino acid sequence of SEQ ID NO: 24.

68. The method of any one of claims 64-67, wherein the second antigen-binding domain of the bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises: (a) three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) contained within a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 20; and (b) three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) contained within a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 24.

69. The method of claim 68, wherein the second antigen-binding domain of the bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 21, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 22, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 23.

70. The method of claim 68 or 69, wherein the second antigen-binding domain of the bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 25, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 26, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 27.

71. The method of any one of claims 68-70, wherein the second antigen-binding domain of the bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 20, and a LCVR comprising the amino acid sequence of SEQ ID NO: 24.

72. The method of any one of claims 64-71, wherein the bispecific anti-MUC16 x anti-CD28 antibody comprises a human IgG heavy chain constant region.

73. The method of claim 72, wherein the human IgG heavy chain constant region is isotype IgG1.

74. The method of claim 72, wherein the human IgG heavy chain constant region is isotype IgG4.

75. The method of claim 73 or 74, wherein the bispecific anti-MUC16 x anti-CD28 antibody comprises a chimeric hinge that reduces Fcɣ receptor binding relative to a wild-type hinge of the same isotype.

76. The method of any one of claims 72-75, wherein the first heavy chain or the second heavy chain of the bispecific anti-MUC16 x anti-CD28 antibody, but not both, comprises a CH3 domain comprising a H435R (EU numbering) modification and a Y436F (EU numbering) modification.

77. The method of any one of claims 64-76, wherein the bispecific anti-MUC16 x anti-CD28 antibody comprises a first heavy chain comprising the amino acid sequence of SEQ ID NO: 28.

78. The method of any one of claims 64-76, wherein the bispecific anti-MUC16 x anti-CD28 antibody comprises a second heavy chain comprising the amino acid sequence of SEQ ID NO: 29.

79. The method of any one of claims 64-76, wherein the bispecific anti-MUC16 x anti-CD28 antibody comprises a first heavy chain comprising the amino acid sequence of SEQ ID NO: 28, a second heavy chain comprising the amino acid sequence of SEQ ID NO: 29, and a common light chain comprising the amino acid sequence of SEQ ID NO: 30.

80. The method of any one of claims 1-79, wherein the bispecific anti-MUC16 x anti- CD28 antibody is administered to the subject at a dose of from 0.01 mg to 1000 mg weekly.

81. The method of claim 80, wherein the anti-MUC16 x anti-CD3 antibody is administered to the subject at a dose of from 0.03 mg to 1000 mg weekly.

82. The method of claim 81, wherein the bispecific anti-MUC16 x anti-CD3 antibody or antigen-binding fragment is administered weekly in a dosing regimen at a dose of 0.1 mg, 0.3 mg, 1 mg, 3 mg, 10 mg, 30 mg, 100 mg, 300 mg, or 1000 mg.

83. The method of claim 81, wherein the bispecific anti-MUC16 x anti-CD28 antibody or antigen-binding fragment is administered weekly in a dosing regimen at a dose of 0.03 mg, 0.1 mg or 0.3 mg during week 5, and at a dose of 0.03 mg, 0.1 mg, 0.3 mg, 1 mg, 10 mg, 100 mg, 300 mg, or 1000 mg during each subsequent week of the dosing regimen.

84. The method of any one of claims 1-83, wherein the subject has stable disease, a partial response, or a complete response following administration of the bispecific anti-MUC16 x anti-CD28 antibody for at least one week at a dose of from 0.03 mg to 1000 mg in combination with the anti-PD-1 antibody or the anti-MUC16 x anti-CD3 antibody.

85. The method of any one of claims 1-84, wherein the bispecific anti-MUC16 x anti- CD28 antibody is REGN5668.