Quinoline derivative used for soft tissue sarcoma combination therapy

Patent metadata

Field	Value
Publication number	US-12377089-B2
Application number	US-202017609990-A
Country	US
Kind code	B2
Filing date	May 11, 2020
Priority date	May 10, 2019
Publication date	Aug 5, 2025
Grant date	Aug 5, 2025

Abstract

A quinoline derivative used for soft tissue sarcoma combination therapy, relating to a use of the quinoline derivative in combination with a second therapeutic drug to treat soft tissue sarcoma, wherein the second therapeutic drug may be a chemotherapy drug, a small molecule targeted anti-tumour drug or an immunotherapy drug. The chemical name of the quinoline derivative compound I is 1-[[[4-(4-fluoro-2-methyl-1H-indol-5-yl)oxy-6-methoxyquinolin-7-yl]oxy]methyl]cyclopropylamine.

First claim

The invention claimed is:

1. A method for treating a soft tissue sarcoma, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of epirubicin,

2. The method according to claim 1 , wherein the soft tissue sarcoma is selected from undifferentiated sarcoma, angiosarcoma, fibrosarcoma, gastrointestinal stromal tumor, leiomyosarcoma, liposarcoma, rhabdomyosarcoma, synovial sarcoma, dermatofibrosarcoma protuberan, malignant peripheral nerve sheath tumor, alveolar soft-part sarcoma, clear cell sarcoma, malignant mesenchymoma, epithelioid sarcoma.

3. The method according to claim 1 , wherein the soft tissue sarcoma is selected from a recurrent soft tissue sarcoma, and/or a metastatic soft tissue sarcoma, and/or a refractory soft tissue sarcoma, and/or an unresectable soft tissue sarcoma, and/or advanced soft tissue sarcoma.

4. The method according to claim 1 , wherein the subject has not previously been treated with systemic chemotherapy, and/or the subject has previously been treated with surgery, radiation therapy, induction chemotherapy, concurrent chemotherapy and/or adjuvant chemotherapy, and/or the subject has not previously been treated with systemic chemotherapy but has been treated with surgery, radiation therapy, induction chemotherapy, concurrent chemotherapy and/or adjuvant chemotherapy, and/or the subject has recurrence of disease progression after achieving complete response following surgery, radiation therapy, induction chemotherapy, concurrent chemotherapy and/or adjuvant chemotherapy, and/or the subject has failed to achieve complete response or partial response following surgery, radiation therapy, induction chemotherapy, concurrent chemotherapy and/or adjuvant chemotherapy, and/or the subject with the cancer metastasizes after the entity has been treated with surgery, radiation therapy, induction chemotherapy, concurrent chemotherapy and/or adjuvant chemotherapy.

5. The method according to claim 1 , wherein the compound of formula I or the pharmaceutically acceptable salt thereof is administered in an intermittent regimen of alternate treatment and interruption periods; wherein the ratio of the treatment period to the interruption period in days is 2:0.5 to 2:5, 2:0.5 to 2:3, 2:0.5 to 2:2, or 2:0.5 to 2:1; and wherein the intermittent regimen is in one of the following cycles: consecutively 2-week treatment and then 2-week interruption, consecutively 2-week treatment and then 1-week interruption, and consecutively 5-day treatment and then 2-day interruption.

6. The method according to claim 1 , wherein the compound of formula I or the pharmaceutically acceptable salt thereof is administered at a daily dose of 3 mg to 30 mg.

7. The method according to claim 1 , comprising administering: (i) a pharmaceutical composition at a dose of 6 mg, 8 mg, 10 mg and/or 12 mg of the compound of formula I or the pharmaceutically acceptable salt thereof; and (ii) a pharmaceutical composition at a dose of 50-150 mg/m 2 of epirubicin.

8. The method according to claim 1 , wherein the soft tissue sarcoma is an undifferentiated pleomorphic sarcoma or alveolar soft-part sarcoma.

9. The method according to claim 1 , wherein the soft tissue sarcoma is selected from desmoid tumor, Kaposi's sarcoma, nerve sheath tumor, pulmonary alveolar soft-part sarcoma, dedifferentiated liposarcoma, myxoid liposarcoma, pleomorphic liposarcoma, mixed-type liposarcoma, low grade fibromyxoid sarcoma, hyalinizing spindle cell tumor, sclerosing epithelioid fibrosarcoma, pericytic tumor, glomus tumor, glomangiomatosis, myopericytoma, myofibroma, angioleiomyoma, embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma, pleomorphic rhabdomyosarcoma, spindle cell/sclerosing rhabdomyosarcoma, epithelioid haemangioendothelioma, epithelioid malignant peripheral nerve sheath tumor, malignant triton tumour, malignant granular cell tumor, synovial sarcoma NOS, synovial sarcoma clear cell sarcoma of soft tissue, desmoplastic small round cell tumor, extra-renal rhabdoid tumor, neoplasms with perivascular epithelioid cell differentiation, intimal sarcoma, unclassified sarcoma, undifferentiated spindle cell sarcoma, undifferentiated round cell sarcoma, undifferentiated epithelioid cell sarcoma, desmoplastic small round cell tumor, low grade fibromyxoid sarcoma, and borderline soft tissue tumor.

10. The method according to claim 1 , wherein the soft tissue sarcoma is locally advanced soft tissue sarcoma.

Assignees

• Chia Tai Tianqing Pharmaceutical Group Co Ltd

Inventors

• Wang Zhiming
• Zhang Shilong
• Zhuang Rongyuan
• Guo Xi
• Wang Yan
• Yang Hua
• Lu Weiqi
• Zhou Yuhong
• Gao Lei

Classifications

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/704

  attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} · CPC title

• A61P35/00 Primary

  Antineoplastic agents · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title

• A61K31/4709 Primary

  Non-condensed quinolines and containing further heterocyclic rings · CPC title