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WO2025082431A1 - Utilisation d'un dérivé d'indole dans le traitement d'une tumeur de la tête et du cou - Google Patents

Utilisation d'un dérivé d'indole dans le traitement d'une tumeur de la tête et du cou Download PDF

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Publication number
WO2025082431A1
WO2025082431A1 PCT/CN2024/125442 CN2024125442W WO2025082431A1 WO 2025082431 A1 WO2025082431 A1 WO 2025082431A1 CN 2024125442 W CN2024125442 W CN 2024125442W WO 2025082431 A1 WO2025082431 A1 WO 2025082431A1
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WO
WIPO (PCT)
Prior art keywords
formula
compound
pharmaceutically acceptable
acceptable salt
pharmaceutical composition
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/CN2024/125442
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English (en)
Chinese (zh)
Inventor
于鼎
李许
汤湧
徐婷
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Chia Tai Tianqing Pharmaceutical Group Co Ltd
Original Assignee
Chia Tai Tianqing Pharmaceutical Group Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Chia Tai Tianqing Pharmaceutical Group Co Ltd filed Critical Chia Tai Tianqing Pharmaceutical Group Co Ltd
Publication of WO2025082431A1 publication Critical patent/WO2025082431A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles

Definitions

  • the present invention belongs to the field of medical technology and relates to the use of an indole derivative in treating head and neck tumors, and specifically relates to the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof in treating head and neck tumors.
  • IAPs apoptosis protein
  • IAP inhibitors have also been found to have certain immunomodulatory effects. Mechanistically, IAP inhibitors can promote the proliferation of CD4+T cells and CD8+T cells, and enhance the activity of these cells. At the same time, IAP inhibitors can also promote T cells and NK cells to secrete cytokines such as IL-2 and IFN- ⁇ , which plays a role in enhancing tumor immunity.
  • Head and neck tumors are one of the most common malignant tumors, which seriously threaten the life and health of patients.
  • the most common pathological type is head and neck squamous cell carcinoma (HNSCC), and other types include head and neck adenocarcinoma, sarcoma and lymphoma.
  • HNSCC head and neck squamous cell carcinoma
  • other types include head and neck adenocarcinoma, sarcoma and lymphoma.
  • the present disclosure provides a compound of formula (I) or a pharmaceutically acceptable salt thereof for use in treating head and neck tumors.
  • the present disclosure provides a pharmaceutical composition for treating head and neck tumors, comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof.
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof described in the present disclosure may be a pharmaceutical composition comprising a therapeutically effective amount of the compound of formula (I) or a pharmaceutically acceptable salt thereof.
  • the pharmaceutical composition contains 50-500 mg, 50-400 mg, 50-300 mg, 50-250 mg, 50-200 mg, 100-200 mg or 150-200 mg of a compound of formula (I) or a pharmaceutically acceptable salt thereof.
  • the pharmaceutical composition contains 50-200 mg, 100-200 mg or 150-200 mg of the compound of formula (I) or a pharmaceutically acceptable salt thereof, calculated as the compound of formula (I).
  • the pharmaceutical composition contains 50 mg, 100 mg, 150 mg, 200 mg, 250 mg or 300 mg of the compound of formula (I) or a pharmaceutically acceptable salt thereof, calculated as the compound of formula (I).
  • the pharmaceutical composition contains 100 mg, 150 mg or 200 mg of the compound of formula (I) or a pharmaceutically acceptable salt thereof, calculated as the compound of formula (I).
  • the pharmaceutical composition contains 200 mg of the compound of formula (I) or a pharmaceutically acceptable salt thereof, calculated as the compound of formula (I).
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered once a day.
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered once a day, and each dose is a single dose or multiple doses, usually multiple doses.
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered once a day, and each dose is multiple doses.
  • the pharmaceutical composition contains a single dose of 50 mg of the compound of formula (I) or a pharmaceutically acceptable salt thereof, calculated as the compound of formula (I).
  • the pharmaceutical composition is in the form of a single administration preparation, and the pharmaceutical composition contains 50 mg of the compound of formula (I) or a pharmaceutically acceptable salt thereof, calculated as the compound of formula (I).
  • one treatment cycle is every 21 or 28 days, preferably one treatment cycle is every 21 days.
  • the pharmaceutical composition is a preparation suitable for administration within a single treatment cycle (e.g., a treatment cycle of 21 days), comprising: a pharmaceutical composition containing a compound of formula (I) or a pharmaceutically acceptable salt thereof, with a total dose of 1050 to 4200 mg (e.g., 1050 mg, 2100 mg, 3150 mg, 4200 mg, or a range formed by any two values) of the compound of formula (I).
  • a single treatment cycle e.g., a treatment cycle of 21 days
  • a pharmaceutical composition containing a compound of formula (I) or a pharmaceutically acceptable salt thereof with a total dose of 1050 to 4200 mg (e.g., 1050 mg, 2100 mg, 3150 mg, 4200 mg, or a range formed by any two values) of the compound of formula (I).
  • the pharmaceutical composition is a preparation suitable for administration within a single treatment cycle (e.g., a treatment cycle of 21 days), and the preparation comprises: a pharmaceutical composition containing a compound of formula (I) or a pharmaceutically acceptable salt thereof, with a total dose of 2100 to 4200 mg (e.g., 2100 mg, 3150 mg, 4200 mg, or a range formed by any two values) of the compound of formula (I).
  • a pharmaceutical composition containing a compound of formula (I) or a pharmaceutically acceptable salt thereof with a total dose of 2100 to 4200 mg (e.g., 2100 mg, 3150 mg, 4200 mg, or a range formed by any two values) of the compound of formula (I).
  • the pharmaceutical composition is a preparation suitable for administration within a single treatment cycle (e.g., a treatment cycle of 21 days), comprising: a pharmaceutical composition containing a compound of formula (I) or a pharmaceutically acceptable salt thereof, with a total dose of 4200 mg calculated as the compound of formula (I).
  • the present disclosure further provides a kit, which contains the compound of formula (I) or a pharmaceutically acceptable salt thereof as described in the present disclosure.
  • the present disclosure also provides a kit of pharmaceutical compositions for treating head and neck tumors, which contains the compound of formula (I) or a pharmaceutically acceptable salt thereof as described in the present disclosure.
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof is prepared into a unit preparation containing 50 mg of the compound of formula (I) or a pharmaceutically acceptable salt thereof, calculated as the compound of formula (I).
  • the present disclosure provides use of a compound of formula (I), a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof in the preparation of a medicament for treating head and neck tumors in a patient.
  • the present disclosure provides a method for treating head and neck tumors, comprising administering a therapeutically effective amount of a compound of formula (I), a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof to a patient in need of treatment, for example, administering a therapeutically effective amount of the pharmaceutical composition described above of the present disclosure to an individual in need thereof.
  • the present disclosure also provides the use of the compound of formula (I) or its pharmaceutically acceptable salt as described above, or its pharmaceutical composition in the preparation of a drug for treating head and neck tumors in patients, for example, the use of the pharmaceutical composition described above in the preparation of a drug for treating head and neck tumors.
  • the present disclosure also provides the use of the compound of formula (I) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for treating head and neck tumors, such as the use of the pharmaceutical composition described above for treating head and neck tumors.
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof is used as a single active agent.
  • the content of the compound of formula (I) or a pharmaceutically acceptable salt thereof in the above-mentioned pharmaceutical composition is a daily dose, which is administered in the following manner: the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered once a day.
  • the content of the compound of formula (I) or its pharmaceutically acceptable salt in the above-mentioned pharmaceutical composition is a daily dose, wherein the compound of formula (I) or its pharmaceutically acceptable salt is administered in a single dose or multiple doses, usually in multiple doses; further, the compound of formula (I) or its pharmaceutically acceptable salt is administered once a day in multiple doses; further, the compound of formula (I) or its pharmaceutically acceptable salt is administered once a day in multiple doses of oral solid preparations.
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered in the following manner: a daily dose of 50-200 mg, 100-200 mg or 150-200 mg.
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered as follows: a daily dose of 100 mg; or, a daily dose of 150 mg; or, a daily dose of 200 mg.
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered in the following manner: a daily dose of 200 mg.
  • the dosage of the compound of formula (I), its pharmaceutically acceptable salt or its pharmaceutical composition is calculated as the compound of formula (I).
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered in multiple doses, and the multiple doses consist of a single dose of 50 mg of the compound of formula (I) or a pharmaceutically acceptable salt thereof.
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered in a continuous daily administration.
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered in a continuous daily administration.
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered in a continuous daily administration in a multiple dose manner.
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered in a continuous daily administration in a multiple dose manner, and the multiple doses consist of a single dose of 50 mg of the compound of formula (I) or a pharmaceutically acceptable salt thereof.
  • the content of the compound of formula (I) or its pharmaceutically acceptable salt is a dose per treatment cycle, which is administered in the following manner: daily administration of the compound of formula (I) or its pharmaceutically acceptable salt.
  • the compound of formula (I) or its pharmaceutically acceptable salt is packaged in a single aliquot or multiple aliquots (e.g., 2 aliquots, 4 aliquots, 7 aliquots, 14 aliquots, 21 aliquots, 28 aliquots or more aliquots).
  • 21 days is a treatment cycle
  • the pharmaceutical composition of the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered daily on days 1 to 14 of each treatment cycle.
  • 21 days is a treatment cycle
  • the pharmaceutical composition of the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered once a day on days 1 to 14 of each treatment cycle.
  • 21 days is a treatment cycle
  • the pharmaceutical composition of the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered once a day continuously on the 1st to 14th days of each treatment cycle
  • each dose of the compound of formula (I) or a pharmaceutically acceptable salt thereof is a multiple dose
  • the multiple doses are 100 mg, 150 mg or 200 mg of the compound of formula (I) or a pharmaceutically acceptable salt thereof; further, the multiple doses are composed of a single dose of 50 mg of the compound of formula (I) or a pharmaceutically acceptable salt thereof.
  • the pharmaceutical composition of the compound of formula (I) or its pharmaceutically acceptable salt is packaged in a kit, which contains 1 day, 2 day, 3 day, 4 day, 5 day, 6 day, 7 day, 8 day, 9 day, 10 day, 11 day, 12 day, 13 day, 14 day, 15 day, 16 day, 17 day, 18 day, 19 day, 20 day, 21 day, 22 day, 23 day, 24 day, 25 day, 26 day, 27 day or 28 day dose, or a dose of the above-mentioned compound of formula (I) or its pharmaceutically acceptable salt or its pharmaceutical composition with any of the foregoing values as endpoints.
  • the pharmaceutical composition of the compound of formula (I) or a pharmaceutically acceptable salt thereof is packaged in a kit, which contains a 1-day, 2-day, 3-day, 4-day, 5-day, 6-day, 7-day, 14-day, 21-day, or 28-day dose, or a dose of the compound of formula (I) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof with any of the foregoing values as endpoints.
  • 21 days is a treatment cycle
  • the total dose of the pharmaceutical composition containing the compound of formula (I) or its pharmaceutically acceptable salt is 1050-4200 mg for continuous daily administration on the 1st to 14th day of each treatment cycle.
  • the total dose of the pharmaceutical composition containing the compound of formula (I) or its pharmaceutically acceptable salt is selected from 1050 mg, 2100 mg, 3150 mg, 4200 mg or the range formed by any two values.
  • the total dose of the pharmaceutical composition containing the compound of formula (I) or its pharmaceutically acceptable salt is selected from 2100 mg, 3150 mg, 4200 mg or the range formed by any two values.
  • the total dose of the pharmaceutical composition containing the compound of formula (I) or its pharmaceutically acceptable salt is selected from 2100 mg, 3150 mg or 4200 mg. In some schemes, the total dose of the pharmaceutical composition containing the compound of formula (I) or its pharmaceutically acceptable salt is selected from 4200 mg.
  • 21 days is a treatment cycle
  • the total dose of the pharmaceutical composition containing the compound of formula (I) or a pharmaceutically acceptable salt thereof, administered once daily continuously from day 1 to day 14 of each treatment cycle is 1050 mg, 2100 mg, 3150 mg, 4200 mg or a range formed by any two of the values.
  • 21 days is a treatment cycle
  • the total dose of the pharmaceutical composition containing the compound of formula (I) or a pharmaceutically acceptable salt thereof administered once daily continuously from day 1 to day 14 of each treatment cycle is 2100 mg, 3150 mg, 4200 mg or a range formed by any two of the values.
  • 21 days is a treatment cycle
  • the total dose of the pharmaceutical composition containing the compound of formula (I) or a pharmaceutically acceptable salt thereof administered once daily continuously from day 1 to day 14 of each treatment cycle is 2100 mg, 3150 mg or 4200 mg.
  • 21 days is a treatment cycle
  • the total dose of the pharmaceutical composition containing the compound of formula (I) or a pharmaceutically acceptable salt thereof administered once daily continuously from day 1 to day 14 of each treatment cycle is 4200 mg.
  • the above treatment cycles are repeated as long as the disease remains under control and the dosing regimen is clinically tolerated.
  • the present disclosure provides a method for treating head and neck tumors, which comprises administering a therapeutically effective amount of a compound of formula (I), a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof to a patient in need of treatment, accompanied by chemoradiotherapy, for example, administering a therapeutically effective amount of the pharmaceutical composition described above of the present disclosure to an individual in need, accompanied by chemoradiotherapy.
  • the present disclosure also provides the use of the compound of formula (I) or its pharmaceutically acceptable salt as described above, or its pharmaceutical composition concomitantly with chemoradiotherapy in the preparation of a medicament for treating head and neck tumors in patients, for example, the use of the pharmaceutical composition described above in the preparation of a medicament for treating head and neck tumors.
  • the present disclosure also provides the use of the compound of formula (I) or its pharmaceutically acceptable salt as described above, or its pharmaceutical composition for treating head and neck tumors concomitantly with chemoradiotherapy, such as the use of the pharmaceutical composition described above for treating head and neck tumors.
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof and the chemoradiotherapy are each in the form of a pharmaceutical composition and can be administered simultaneously, separately, concurrently, sequentially or intermittently.
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof and the chemotherapy are each in the form of a pharmaceutical composition and can be administered simultaneously, separately, concurrently, sequentially or intermittently.
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof and chemoradiotherapy have the same or different treatment cycles, respectively.
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof and chemoradiotherapy have the same treatment cycle, respectively.
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof and chemotherapy have the same treatment cycle, respectively, and the treatment cycle is 1 treatment cycle every 3 weeks.
  • the radiotherapy starts on day 1, with conventional fractionation, and is usually completed in 6 to 7 weeks.
  • the administration method of the compound of formula (I) or its pharmaceutically acceptable salt or its pharmaceutical composition is as described above.
  • the chemoradiotherapy refers to chemotherapy drug therapy and radiation therapy.
  • the chemotherapy drug is selected from one or a combination of two or more of cisplatin, carboplatin, docetaxel, paclitaxel, 5-fluorouracil, gemcitabine, capecitabine, and methotrexate; preferably, one or a combination of two or more of cisplatin, carboplatin, paclitaxel, and 5-fluorouracil; further preferably, cisplatin, carboplatin, or paclitaxel; and even more preferably, cisplatin.
  • the cumulative dose of the chemotherapeutic drug is 200 mg/ m2 or more.
  • the radiotherapy dose is 66 to 75 Gy, preferably 66 to 70 Gy.
  • the pharmaceutical composition of the compound of formula (I) or a pharmaceutically acceptable salt thereof continues to be administered alone after the end of chemoradiotherapy, and the administration method of the compound of formula (I) or a pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof is as described above.
  • the pharmaceutical composition of the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered for a total of 7 cycles, and the administration method of the compound of formula (I) or a pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof is as described above.
  • the pharmaceutical composition of the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered concurrently with chemoradiotherapy for a total of 2-3 cycles, and is continued to be administered alone for 4-5 cycles after the end of chemoradiotherapy.
  • the administration method of the compound of formula (I) or a pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof is as described above.
  • the amount of the compound of formula (I) or a pharmaceutically acceptable salt thereof administered can be determined based on the severity of the disease, the response of the disease, any treatment-related toxicity, and the age and health status of the patient.
  • the dosage and administration cycle of chemotherapy drugs and radiotherapy can be adjusted according to the subject's tolerance and adverse reaction level, and can be further determined in combination with the commonly used treatment options in the head and neck tumor diagnosis and treatment guidelines.
  • the head and neck tumor is a locally advanced head and neck tumor.
  • the head and neck tumor is a locally advanced head and neck tumor that is treated non-surgically.
  • the head and neck tumor is a locally advanced head and neck tumor that is confirmed by pathological histological examination and is a candidate for non-surgical treatment.
  • the head and neck tumors include but are not limited to squamous cell carcinoma of the head and neck (SCCHN) and/or head and neck glandular tumors.
  • the head and neck tumor is locally advanced head and neck squamous cell carcinoma that is treated non-surgically.
  • the head and neck tumor is a locally advanced head and neck glandular tumor that is treated non-surgically.
  • the head and neck squamous cell carcinoma does not include nasopharyngeal carcinoma.
  • the head and neck glandular tumor does not include thyroid cancer.
  • the head and neck glandular tumor is selected from head and neck adenocarcinoma and adenoid cystic carcinoma.
  • the primary site of head and neck squamous cell carcinoma is selected from the oropharynx, oral cavity, hypopharynx or larynx.
  • the head and neck squamous cell carcinoma is selected from hypopharyngeal cancer, tongue cancer, oral cancer, oropharyngeal cancer, or laryngeal cancer.
  • the head and neck squamous cell carcinoma is selected from hypopharyngeal cancer, tongue cancer, oral cancer, or oropharyngeal cancer.
  • the head and neck glandular tumor is adenoid cystic carcinoma.
  • the head and neck glandular tumor is adenoid cystic carcinoma of the base of the tongue.
  • the TNM stage of the head and neck tumor is stage IVA or stage IVB.
  • the IVA stage includes T being T1-3, N being N2, and M being M0; or the IVA stage includes T being T4a, N being N0-2, and M being M0.
  • the IVB stage includes T being T4b, N being any N, and M being M0; or the IVB stage The term includes T being any T, N being N3, and M being M0.
  • the N2 includes N2a, N2b or N2c.
  • the N3 includes N3a or N3b.
  • the TNM stage of head and neck squamous cell carcinoma is IVA or IVB.
  • the TNM stage of the head and neck glandular tumor is IVA or IVB.
  • the head and neck cancer patients are patients with locally advanced head and neck cancer who are receiving non-surgical treatment and concurrent cisplatin-based chemoradiotherapy.
  • the head and neck tumor patient has at least one measurable lesion (RECIST 1.1) before radiotherapy.
  • RECIST 1.1 measurable lesion
  • the head and neck cancer patient has not previously received any systemic treatment for locally advanced head and neck cancer or radiation therapy for target lesions.
  • the head and neck tumor patient may have undergone a single surgical treatment and local recurrence in the past, and meet any one or more of the following conditions: (1) only underwent a single surgical treatment and remained disease-free for more than 6 months after the surgery; (2) the current recurrent lesion stage is IVA or IVB; (3) only underwent one surgical treatment.
  • the efficacy of the disclosed head and neck tumor patients is evaluated once every 2 cycles, and after 8 cycles, it is extended to once every 4 cycles.
  • the compound of formula (I) or its pharmaceutically acceptable salt can be administered by a variety of routes, including but not limited to the following routes: oral, parenteral, intraperitoneal, intravenous, intraarterial, transdermal, sublingual, intramuscular, rectal, transbuccal, intranasal, by inhalation, vaginal, intraocular, by topical administration, subcutaneous, intrafatty, intraarticular, intraperitoneal and intrathecal.
  • routes including but not limited to the following routes: oral, parenteral, intraperitoneal, intravenous, intraarterial, transdermal, sublingual, intramuscular, rectal, transbuccal, intranasal, by inhalation, vaginal, intraocular, by topical administration, subcutaneous, intrafatty, intraarticular, intraperitoneal and intrathecal.
  • routes including but not limited to the following routes: oral, parenteral, intraperitoneal, intravenous, intraarterial, transdermal, sublingual, intramuscular, rectal,
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered in a continuous daily oral administration manner.
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered once a day in the form of multiple doses of an oral solid preparation.
  • the compounds of formula (I) disclosed herein can be administered in the form of their free base, or in the form of their pharmaceutically acceptable salts, hydrates, and prodrugs, which are converted into the form of the compounds of formula (I) in vivo.
  • pharmaceutically acceptable salts of the compounds of formula (I) are within the scope of the present disclosure, and the salts can be produced from various organic acids and inorganic acids according to methods known in the art.
  • the molar ratio of the compounds of formula (I) to the acid ions forming the pharmaceutically acceptable salts may be 1:1.
  • the dosage of the compound of formula (I) or its pharmaceutically acceptable salt referred to in the present disclosure is based on the amount of the compound of formula (I) unless otherwise stated.
  • the pharmaceutically acceptable salt of the compound of formula (I) exists in the form of a salt of the compound of formula (I).
  • a single dose of the pharmaceutical composition of the compound of formula (I) or a pharmaceutically acceptable salt thereof is 50 mg calculated as the compound of formula (I).
  • the pharmaceutical composition of the compound of formula (I) or a pharmaceutically acceptable salt thereof is prepared as a unit preparation containing 50 mg of the compound of formula (I) or a pharmaceutically acceptable salt thereof calculated as the compound of formula (I).
  • the method of administration can be determined comprehensively based on the activity, toxicity and patient tolerance of the drug.
  • the pharmaceutical composition containing the compound of formula (I) or a pharmaceutically acceptable salt thereof further contains a pharmaceutically acceptable excipient.
  • Pharmaceutically acceptable excipients include fillers, absorbents, wetting agents, adhesives, disintegrants, lubricants, etc.
  • the pharmaceutical composition includes but is not limited to preparations suitable for oral, parenteral, and topical administration.
  • the pharmaceutical composition is a preparation suitable for oral administration.
  • the pharmaceutical composition is a solid preparation suitable for oral administration.
  • the pharmaceutical composition includes but is not limited to tablets and capsules.
  • the pharmaceutical composition is a solid pharmaceutical combination.
  • the pharmaceutical composition of the compound of formula (I) or a pharmaceutically acceptable salt thereof is a solid pharmaceutical composition containing the compound of formula (I) or a pharmaceutically acceptable salt thereof.
  • the pharmaceutical composition of the compound of formula (I) or a pharmaceutically acceptable salt thereof is a tablet containing the compound of formula (I) or a pharmaceutically acceptable salt thereof.
  • the pharmaceutical composition of the present disclosure can be manufactured by methods well known in the art, such as conventional mixing methods, dissolving methods, granulating methods, making dragees, grinding methods, emulsifying methods, freeze-drying methods, and the like.
  • Solid oral compositions can be prepared by conventional mixing, filling or tableting methods. For example, they can be obtained by mixing the active compound with a solid excipient, optionally grinding the resulting mixture, adding other suitable excipients if necessary, and then processing the mixture into particles to obtain a tablet or a dragee core.
  • suitable excipients include, but are not limited to, adhesives, diluents, disintegrants, lubricants, glidants, sweeteners or flavoring agents, etc.
  • the "clinical benefits" of the compounds of formula (I) disclosed herein include, but are not limited to: a higher 18-month disease-free survival rate (18m-DFS) of clinical patients, a prolonged overall survival (OS), a higher objective response rate (ORR), a higher disease control rate (DCR), a longer duration of disease remission (DOR), a better 18-month regional control rate, a reduction in the number and/or severity of adverse reactions, a decrease in distant metastasis rate and local control rate, etc.
  • m-DFS 18-month disease-free survival rate
  • OS overall survival
  • ORR objective response rate
  • DCR disease control rate
  • DOR longer duration of disease remission
  • a better 18-month regional control rate a reduction in the number and/or severity of adverse reactions, a decrease in distant metastasis rate and local control rate, etc.
  • patient or “individual/subject” refers to a mammal, such as a primate (human, macaque, chimpanzee, etc.), a rodent (mice, rats, rabbits, etc.), a cat, a canine, etc., preferably a human.
  • a primate human, macaque, chimpanzee, etc.
  • a rodent mice, rats, rabbits, etc.
  • a cat preferably a human.
  • the patient and the individual are patients who have not previously received systemic treatment for locally advanced head and neck tumors or radiation therapy for target lesions.
  • pharmaceutically acceptable refers to a carrier, excipient or excipient used to prepare a pharmaceutical composition, which is generally safe, non-toxic and not biologically or otherwise undesirable, and includes those that are acceptable for use in human medicine.
  • pharmaceutically acceptable salt includes, but is not limited to, acid addition salts formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or acid addition salts formed with organic acids such as acetic acid, trifluoroacetic acid, propionic acid, hexanoic acid, heptanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, p-chlorobenzenesulfonic acid, p-toluenes
  • terapéuticaally effective amount means the amount of a compound that, when administered to a human for treating a disease, is sufficient to effect treatment for the disease.
  • treatment means administering the compounds or formulations disclosed herein to improve, alleviate or eliminate a disease or one or more symptoms associated with the disease, and includes: (i) inhibiting a disease or disease state, i.e., curbing or delaying its development; (ii) alleviating a disease or disease state, i.e., causing the disease or disease state to regress.
  • an "adverse event” is any unfavorable and generally unintended or unwanted sign (including abnormal laboratory findings), symptom, or disease associated with the use of a medical treatment.
  • an adverse event may be associated with activation of the immune system or expansion of immune system cells (e.g., T cells) in response to a treatment.
  • a medical treatment may have one or more associated AEs, and each AE may have Same or different severity levels.
  • Reference to a method that is capable of "modifying an adverse event” refers to a therapeutic regimen that reduces the incidence and/or severity of one or more AEs associated with the use of a different therapeutic regimen.
  • DLT dose-limiting toxicity
  • Grade 3 toxicity regardless of duration, except for the following: 1 Grade 3 diarrhea, nausea, and vomiting that improve to Grade 2 or below within 3 days after supportive treatment; 2 Grade 3 fatigue lasting less than 7 days; 3 Transient Grade 3 hypotension (based on the mechanism of action of this type of drug, it may lead to increased cytokines and subsequent hypotension. Grade 3 hypotension can be relieved by giving ⁇ 3L of intravenous fluid infusion within 8 hours after administration).
  • Grade 4 neutropenia lasting for more than 7 days; 2) Grade 3 febrile neutropenia (ANC ⁇ 1000/mm3, body temperature exceeds 38.3°C for one time or body temperature remains ⁇ 38°C for more than one hour) or Grade 4 febrile neutropenia; 3) Grade 3 thrombocytopenia with bleeding; 4) Grade 4 thrombocytopenia; 5) Other hematological toxicities of Grade 4 or above.
  • the “maximum tolerated dose” (MTD) used in this article refers to the highest dose in which less than 33% of the subjects experience DLT in the first cycle.
  • MTD maximum tolerated dose
  • pharmaceutically acceptable excipients refers to those excipients that have no significant irritation to the organism and do not impair the biological activity and performance of the active compound. Suitable excipients are well known to those skilled in the art, such as carbohydrates, waxes, water-soluble and/or water-swellable polymers, hydrophilic or hydrophobic materials, gelatin, oils, solvents, water, etc.
  • administering and “administering” refer to the physical introduction of a composition comprising a therapeutic agent into a subject using any of a variety of methods and delivery systems known to those skilled in the art.
  • administration is oral administration.
  • daily dose refers to the dose administered to a patient daily.
  • single dose or "unit preparation” refers to the smallest packaging unit of a drug containing a certain amount of active ingredient. For example, if a box of medicine contains seven capsules, each capsule is a single dose or unit preparation; for example, if a box of medicine contains seven tablets, each tablet is a single dose unit preparation.
  • multiple doses consists of multiple single doses.
  • “combination”, “combination” or “combined use” means that two or more active substances can be administered to an individual simultaneously, concurrently or sequentially in any order, each as a single formulation.
  • pharmaceutical composition refers to a mixture of one or more active ingredients of the present disclosure or a pharmaceutical combination thereof and pharmaceutically acceptable excipients.
  • the purpose of a pharmaceutical composition is to facilitate administration of the compounds of the present disclosure or a pharmaceutical combination thereof to an individual.
  • day When referring to a dosing regimen, the terms "day,” “daily,” and the like refer to the times within a calendar day, beginning at midnight and ending at the following midnight.
  • recurrent cancer is a cancer that grows back in the original site or at a distant site after responding to initial treatment (eg, surgery).
  • a "locally recurrent” cancer is a cancer that appears after treatment in the same location as a previously treated cancer.
  • the parameter values representing the amount of ingredients or physicochemical properties or reaction conditions should be understood to be the same in all cases.
  • the term “about” indicates that there is an error value, for example, it indicates a change within the range of ⁇ 5%, such as ⁇ 1% or ⁇ 0.1% of a particular value.
  • Cal27 cells were subcutaneously inoculated in the right axilla of SPF male nude mice (source: Changzhou Cavens Laboratory Animal Co., Ltd.), 5 ⁇ 10 6 cells/mouse. When the average tumor volume reached about 100 mm 3 , the animals were divided into groups.
  • the day of grouping was day 0. From day 0 onwards, drugs were administered by gavage once a day. Tumor volume was measured 2-3 times a week, and the mice were weighed and the data were recorded. The general performance of the mice was observed and recorded daily. After the experiment, the tumor was removed, weighed, and photographed.
  • the detection indicators and calculation formula are as follows:
  • Tumor volume, TV (mm 3 ) 1/2 ⁇ (a ⁇ b 2 ); where a is the long diameter of the tumor, and b is the short diameter of the tumor.
  • T/C (%) TRTV / CRTV ⁇ 100%;
  • TRTV is the RTV of the treatment group;
  • CRTV is the RTV of the vehicle control group.
  • TGI (%) (1-TW/TW 0 ) ⁇ 100%; wherein, TW is the tumor weight of the treatment group, and TW 0 is the tumor weight of the vehicle control group.
  • Body weight change rate, WCR (%) (Wt t - Wt 0 )/Wt 0 ⁇ 100%; wherein Wt 0 is the body weight of mice on day 0, and Wt t is the body weight of mice at each measurement.
  • test results show that the compound of formula (I) can effectively inhibit the tumor growth of Cal27 human tongue squamous cell carcinoma nude mice, showing good drug efficacy.
  • FaDu cells were subcutaneously inoculated in the right axilla of SPF male nude mice (source: Changzhou Cavens Laboratory Animal Co., Ltd.), 5 ⁇ 10 6 cells/mouse. When the average tumor volume reached about 100 mm 3 , the animals were divided into groups.
  • the day of grouping was day 0. From day 0 onwards, drugs were administered by gavage once a day. Tumor volume was measured 2-3 times a week, and the mice were weighed and the data were recorded. The general performance of the mice was observed and recorded daily. After the experiment, the tumor was removed, weighed, and photographed.
  • the detection indicators and calculation formula are as follows:
  • Tumor volume, TV (mm 3 ) 1/2 ⁇ (a ⁇ b 2 ); where a is the long diameter of the tumor, and b is the short diameter of the tumor.
  • T/C (%) TRTV / CRTV ⁇ 100%;
  • TRTV is the RTV of the treatment group;
  • CRTV is the RTV of the vehicle control group.
  • TGI (%) (1-TW/TW 0 ) ⁇ 100%; wherein, TW is the tumor weight of the treatment group, and TW 0 is the tumor weight of the vehicle control group.
  • Body weight change rate, WCR (%) (Wt t - Wt 0 )/Wt 0 ⁇ 100%; wherein Wt 0 is the body weight of mice on day 0, and Wt t is the body weight of mice at each measurement.
  • test results show that the compound of formula (I) can effectively inhibit the tumor growth of FaDu human pharyngeal squamous cell carcinoma nude mice, showing good drug efficacy.
  • SCC25 cells were subcutaneously inoculated in the right axilla of SPF male nude mice (source: Changzhou Cavens Laboratory Animal Co., Ltd.), 5 ⁇ 10 6 cells/mouse. When the average tumor volume reached about 70 mm 3 , the animals were divided into groups.
  • the day of grouping was day 0. From day 0 onwards, drugs were administered by gavage once a day. Tumor volume was measured 2-3 times a week, and the mice were weighed and the data were recorded. The general performance of the mice was observed and recorded daily. After the experiment, the tumor was removed, weighed, and photographed.
  • the detection indicators and calculation formula are as follows:
  • Tumor volume, TV (mm 3 ) 1/2 ⁇ (a ⁇ b 2 ); where a is the long diameter of the tumor, and b is the short diameter of the tumor.
  • T/C (%) TRTV / CRTV ⁇ 100%;
  • TRTV is the RTV of the treatment group;
  • CRTV is the RTV of the vehicle control group.
  • TGI (%) (1-TW/TW 0 ) ⁇ 100%; wherein, TW is the tumor weight of the treatment group, and TW 0 is the tumor weight of the vehicle control group.
  • Body weight change rate, WCR (%) (Wt t - Wt 0 )/Wt 0 ⁇ 100%; wherein Wt 0 is the body weight of mice on day 0, and Wt t is the body weight of mice at each measurement.
  • test results show that the compound of formula (I) can effectively inhibit the tumor growth of SCC25 human oral squamous cell carcinoma/human tongue squamous cell carcinoma nude mice, showing good drug efficacy.
  • the Phase Ib dose escalation phase will enroll patients with locally advanced head and neck tumors who are not treated surgically to evaluate the preliminary efficacy, safety and tolerability of the tablets of the compound of formula (I) in subjects with locally advanced head and neck tumors who are not treated surgically and are receiving concurrent chemoradiotherapy, and to determine the recommended dose for Phase II.
  • Phase II adopts a parallel control study. Subjects with locally advanced head and neck squamous cell carcinoma who meet the inclusion criteria after screening will be randomly divided into the experimental group (cohort one) and the control group (cohort two); subjects with locally advanced head and neck glandular tumors who meet the inclusion criteria after screening will enter the exploratory group (cohort three). The details are as follows:
  • Control group (cohort 2): concurrent platinum-containing chemoradiotherapy.
  • Exploratory group (cohort three): receiving compound of formula (I) tablets + concurrent platinum-containing chemoradiotherapy.
  • Age 18-70 years old (when signing the informed consent form), gender is not limited;
  • the expected survival period is more than 3 months
  • Cisplatin 80-100 mg/m 2 each time, starting from day 1, one cycle is 3 weeks, for a total of 3 cycles.
  • Radiotherapy The recommended radiotherapy dose is 66-70 Gy.
  • the minimum technical standard for radiotherapy is intensity-modulated radiotherapy (IMRT). Radiotherapy starts on the first day, with conventional fractionation, and is completed in 6-7 weeks.
  • IMRT intensity-modulated radiotherapy
  • Effectiveness evaluation criteria RECIST 1.1 standard was used to determine the disease status.
  • Safety evaluation criteria The severity of adverse events is determined using the NCI-CTC AE 5.0 standard. During the trial, the adverse event record form should be filled in truthfully, including the time of occurrence, severity, relevance to the study treatment, duration, measures taken, and outcomes of the adverse event.
  • Safety Mainly grade 1 to 2, controllable after symptomatic treatment, no DLT events, and overall safety is good.
  • test results show that the recommended dose of the compound of formula (I), its pharmaceutically acceptable salt or its pharmaceutical composition in the Phase II clinical trial is 200 mg based on the compound of formula (I).

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Abstract

L'invention concerne l'utilisation d'un dérivé d'indole pour traiter une tumeur de la tête et du cou, spécifiquement l'utilisation d'un composé représenté par la formule (I), un sel pharmaceutiquement acceptable de celui-ci, ou une composition pharmaceutique de celui-ci dans le traitement d'une tumeur de la tête et du cou. Le composé représenté par la formule (I) présente une bonne efficacité dans la réduction de la croissance tumorale ou même l'élimination de tumeurs.
PCT/CN2024/125442 2023-10-18 2024-10-17 Utilisation d'un dérivé d'indole dans le traitement d'une tumeur de la tête et du cou Pending WO2025082431A1 (fr)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1153518A (zh) * 1994-05-09 1997-07-02 万有制药株式会社 抗肿瘤吲哚并吡咯并咔唑衍生物
US20030191162A1 (en) * 1998-12-31 2003-10-09 Sugen Inc. 3-heteroarylidenyl-2-indolinone compounds for modulating protein kinase activity and for use in cancer chemotherapy
WO2009006839A1 (fr) * 2007-07-11 2009-01-15 Medical College Of Chinese People`S Armed Police Force Dérivés d'indol-3-yl oxalylpodophyllotoxine substitués, leurs sels et leur application
WO2020057536A1 (fr) * 2018-09-18 2020-03-26 正大天晴药业集团股份有限公司 Dérivé de quinoléine pour le traitement d'une tumeur cérébrale
WO2020233723A1 (fr) * 2019-05-23 2020-11-26 正大天晴药业集团股份有限公司 Dérivés de quinoléine pour le traitement du cancer de la tête et du cou
CN114685602A (zh) * 2017-11-13 2022-07-01 正大天晴药业集团股份有限公司 用作iap抑制剂的smac模拟物及其用途

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1153518A (zh) * 1994-05-09 1997-07-02 万有制药株式会社 抗肿瘤吲哚并吡咯并咔唑衍生物
US20030191162A1 (en) * 1998-12-31 2003-10-09 Sugen Inc. 3-heteroarylidenyl-2-indolinone compounds for modulating protein kinase activity and for use in cancer chemotherapy
WO2009006839A1 (fr) * 2007-07-11 2009-01-15 Medical College Of Chinese People`S Armed Police Force Dérivés d'indol-3-yl oxalylpodophyllotoxine substitués, leurs sels et leur application
CN114685602A (zh) * 2017-11-13 2022-07-01 正大天晴药业集团股份有限公司 用作iap抑制剂的smac模拟物及其用途
WO2020057536A1 (fr) * 2018-09-18 2020-03-26 正大天晴药业集团股份有限公司 Dérivé de quinoléine pour le traitement d'une tumeur cérébrale
WO2020233723A1 (fr) * 2019-05-23 2020-11-26 正大天晴药业集团股份有限公司 Dérivés de quinoléine pour le traitement du cancer de la tête et du cou

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DONG XIAO-CHUN, ZHOU FU-SHENG,ZHENG JIAN-BIN,WEN REN: "Synthesis of 1-furfuryl-indolin-2-one derivatives and preliminary evaluation of their antitumor activities", ACTA PHARMACEUTICA SINICA, vol. 43, no. 1, 12 January 2008 (2008-01-12), CN , pages 54 - 59, XP093306400, ISSN: 0513-4870, DOI: 10.16438/j.0513-4870.2008.01.014 *
PACHE LARS; DUTRA MIRIAM S.; SPIVAK ADAM M.; MARLETT JOHN M.; MURRY JEFFREY P.; HWANG YOUNG; MAESTRE ANA M.; MANGANARO LARA; VAMOS: "BIRC2/cIAP1 Is a Negative Regulator of HIV-1 Transcription and Can Be Targeted by Smac Mimetics to Promote Reversal of Viral Latency", CELL HOST & MICROBE, vol. 18, no. 3, 10 September 2015 (2015-09-10), NL , pages 345 - 353, XP029268038, ISSN: 1931-3128, DOI: 10.1016/j.chom.2015.08.009 *

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