EP-4740946-A1 - METHOD FOR TREATING PROSTATE CANCER

Abstract

A method for treating prostate cancer; specifically, the use of a compound of formula I or a pharmaceutically acceptable salt thereof in the preparation of a drug for treating metastatic castration-resistant prostate cancer.

Inventors

• WANG, WENLIANG

Assignees

• Jiangsu Hengrui Pharmaceuticals Co., Ltd.
• Shanghai Shengdi Pharmaceutical Co., Ltd

Dates

Publication Date

20260513

Application Date

20240705

Claims (8)

1. Use of a compound of formula I or a pharmaceutically acceptable salt thereof in the preparation of a drug for treating metastatic castration-resistant prostate cancer
2. The use according to claim 1, characterised in that the metastatic castration-resistant prostate cancer is metastatic castration-resistant prostate cancer that has been treated with medical castration or surgical castration, or has maintained effective LHRHA therapy without bilateral orchidectomy.
3. The use according to claim 1, characterised in that the metastatic castration-resistant prostate cancer is metastatic castration-resistant prostate cancer that has failed at least one prior endocrine drug therapy; and the endocrine drug is preferably abiraterone, enzalutamide, apalutamide, rezvilutamide or darolutamide.
4. The use according to claim 1, characterised in that the metastatic castration-resistant prostate cancer is metastatic castration-resistant prostate cancer that has been previously treated with at least one chemotherapeutic drug and has progressed during chemotherapy or within 6 months after chemotherapy, or is unsuitable for or intolerant to a chemotherapeutic drug; the chemotherapeutic drug is preferably a taxane-based chemotherapeutic drug, and more preferably docetaxel.
5. The use according to claim 1, characterised in that the subject for administration of the compound of formula I or the pharmaceutically acceptable salt thereof is a human.
6. The use according to claim 1, characterised in that the compound of formula I or the pharmaceutically acceptable salt thereof is administered at a dose of 10 mg-1000 mg.
7. The use according to claim 1, characterised in that the compound of formula I or the pharmaceutically acceptable salt thereof is administered at a dose of 30 mg, 90 mg, 180 mg, 360 mg, 540 mg or 720 mg.
8. The use according to claim 1, characterised in that the compound of formula I or the pharmaceutically acceptable salt thereof has a unit dose of 10 mg-300 mg.

Description

Technical Field The present application relates to the field of medicine, and includes the use of a compound of formula I or a pharmaceutically acceptable salt thereof in the preparation of a drug for treating prostate cancer. Background Art Androgen receptor (AR) is a ligand-dependent transcriptional regulatory protein that belongs to the nuclear receptor superfamily and is mainly found in the nucleus. AR that is not bound to the ligand binds to heat shock protein (HSP); however, after AR binds to the ligand, it undergoes a conformational change and dissociates from the HSP, and exhibits increased affinity for DNA (the activation of AR). Activated AR binds in dimer form to a specific DNA sequence in the nucleus (i.e., androgen response element, ARE) and interacts with other transcription factors, thereby regulating the expression of relevant genes and producing biological effects. Studies have shown that abnormalities in the AR signalling pathway are closely related to the development and progression of diseases such as prostate cancer, benign prostatic hyperplasia, Kennedy's disease, male infertility, androgen insensitivity syndrome, and male breast cancer. Prostate cancer is one of the most common malignancies. According to statistics, in 2018, there were nearly 1.3 million new cases and 359,000 deaths worldwide, accounting for 13.5% of the incidence of malignancies in men, ranking second, and 6.7% of the mortality of malignancies in men, ranking fifth. At present, the incidence of prostate cancer is increasing annually, and making it a major cause of death among male cancer patients. A number of AR antagonists (e.g., the first generation AR inhibitor bicalutamide, and the second generation AR inhibitors enzalutamide and rezvilutamide) have been approved for marketing, successfully used in the treatment of hormone-sensitive and castration-resistant prostate cancer, and have become a major treatment for prostate cancer. Although the development and application of the new AR-targeted drugs have significantly improved the prognosis of patients with prostate cancer, particularly providing alternative treatment options other than chemotherapy for patients with mCRPC, patients still may develop resistance to the novel AR-targeted drugs. Summary of the Invention The present disclosure provides a compound of formula I or a pharmaceutically acceptable salt thereof for treating metastatic castration-resistant prostate cancer, In certain embodiments, the present disclosure provides a method of treating metastatic castration-resistant prostate cancer, the method comprising administering to a patient a therapeutically effective amount of the compound of formula I or the pharmaceutically acceptable salt thereof. In certain embodiments, the present disclosure provides a method of treating metastatic castration-resistant prostate cancer, the method comprising administering to a patient a therapeutically effective amount of the compound of formula I or the pharmaceutically acceptable salt thereof after a meal. The present disclosure also provides a method of treating metastatic castration-resistant prostate cancer, the method comprising administering to a patient a therapeutically effective amount of the compound of formula I or the pharmaceutically acceptable salt thereof and a therapeutically effective amount of a CYP3A4 enzyme substrate. In certain embodiments, the method for treating metastatic castration-resistant prostate cancer described in the present disclosure, which comprises administering to the patient a therapeutically effective amount of the compound of formula I or the pharmaceutically acceptable salt thereof and a therapeutically effective amount of a CYP3A4 enzyme substrate, does not require adjustment of the administration dose of the compound of formula I or the pharmaceutically acceptable salt thereof. In certain embodiments, the CYP3A4 enzyme substrate described in the present disclosure is midazolam. In certain embodiments, the metastatic castration-resistant prostate cancer described in the present disclosure is metastatic castration-resistant prostate cancer that has been treated with medical castration or surgical castration. In certain embodiments, the metastatic castration-resistant prostate cancer described in the present disclosure is selected from metastatic castration-resistant prostate cancer that has been treated with continuous luteinizing hormone-releasing hormone analogue (LHRHA) (medical castration), or has previously undergone bilateral orchidectomy (surgical castration), or has maintained effective LHRHA therapy without bilateral orchidectomy. In certain embodiments, the patient with metastatic castration-resistant prostate cancer described in the present disclosure has a castrate level of testosterone (≦50 ng/dL or 1.73 nmol/L). In certain embodiments, the metastatic castration-resistant prostate cancer described in the present disclosure is metastatic castration-resistant prostat