A combination of estrogen receptor degraders and CDK4 inhibitors.

Abstract

Disclosed herein are methods for treating cancer, comprising the step of administering to a subject compound A, or a pharmaceutically acceptable salt thereof, in combination with a selective CDK4 inhibitor. [Formula 1] TIFF2026519559000029.tif71140 [Figure 1] TIFF2026519559000030.tif91132

Claims

1. A method for treating cancer, and for the subject, 【Chemistry 1】 A method comprising the step of administering a compound A having the structure of, or a pharmaceutically acceptable salt thereof, in combination with a selective CDK4 inhibitor.

2. The method according to claim 1, wherein a daily dose of compound A, or a pharmaceutically acceptable salt thereof, is administered to the subject.

3. The method according to claim 2, wherein the daily dose of compound A, or a pharmaceutically acceptable salt thereof, is about 200 mg.

4. The method according to claim 2, wherein the daily dose of compound A, or a pharmaceutically acceptable salt thereof, is about 100 mg.

5. The method according to any one of claims 1 to 4, wherein the daily dose of compound A, or a pharmaceutically acceptable salt thereof, is administered once daily (QD).

6. The method according to any one of claims 1 to 5, wherein the selective CDK4 inhibitor is administered concurrently or sequentially.

7. The method according to any one of claims 1 to 6, wherein compound A, or a pharmaceutically acceptable salt thereof, is administered daily in a 28-day cycle, and the selective CDK4 inhibitor is administered once or twice daily for each 28-day cycle.

8. The method according to any one of claims 1 to 6, wherein the selective CDK4 inhibitor is administered intermittently.

9. The method according to any one of claims 1 to 8, wherein the daily dose of compound A, or a pharmaceutically acceptable salt thereof, is administered orally to the subject.

10. The method according to any one of claims 1 to 9, wherein the subject is the feeding situation.

11. The method according to any one of claims 1 to 10, wherein the selective CDK4 inhibitor is 1,5-anhydro-3-({5-chloro-4-[4-fluoro-2-(2-hydroxypropan-2-yl)-1-(propan-2-yl)-1H-benzimidazole-6-yl]pyrimidine-2-yl}amino)-2,3-dideoxy-D-threopentitol, or a solvate (e.g., hydrate) or a pharmaceutically acceptable salt thereof.

12. The method according to claim 11, wherein a daily dose of 1,5-anhydro-3-({5-chloro-4-[4-fluoro-2-(2-hydroxypropan-2-yl)-1-(propan-2-yl)-1H-benzimidazole-6-yl]pyrimidine-2-yl}amino)-2,3-dideoxy-D-threopentitol, or a solvate (e.g., hydrate) or a pharmaceutically acceptable salt thereof, is administered to the subject.

13. The method according to claim 12, wherein the daily dose of 1,5-anhydro-3-({5-chloro-4-[4-fluoro-2-(2-hydroxypropan-2-yl)-1-(propan-2-yl)-1H-benzimidazole-6-yl]pyrimidine-2-yl}amino)-2,3-dideoxy-D-threopentitol, or a solvate (e.g., hydrate) or a pharmaceutically acceptable salt thereof is about 100 mg.

14. The method according to claim 12, wherein the daily dose of 1,5-anhydro-3-({5-chloro-4-[4-fluoro-2-(2-hydroxypropan-2-yl)-1-(propan-2-yl)-1H-benzimidazole-6-yl]pyrimidine-2-yl}amino)-2,3-dideoxy-D-threopentitol, or a solvate (e.g., hydrate) or a pharmaceutically acceptable salt thereof is about 300 mg.

15. The method according to claim 13 or claim 14, wherein the daily dose of 1,5-anhydro-3-({5-chloro-4-[4-fluoro-2-(2-hydroxypropan-2-yl)-1-(propan-2-yl)-1H-benzimidazole-6-yl]pyrimidine-2-yl}amino)-2,3-dideoxy-D-threopentitol, or a solvate (e.g., hydrate) or a pharmaceutically acceptable salt thereof, is administered twice daily (BID).

16. The method according to any one of claims 1 to 15, wherein the cancer is breast cancer, lung cancer, colon cancer, brain tumor, head and neck cancer, prostate cancer, stomach cancer, pancreatic cancer, ovarian cancer, melanoma, endocrine cancer, uterine cancer, testicular cancer, or bladder cancer.

17. The method according to claim 16, wherein the cancer is breast cancer, lung cancer, prostate cancer, pancreatic cancer, or ovarian cancer.

18. The method according to claim 17, wherein the cancer is breast cancer, lung cancer, or prostate cancer.

19. The method according to claim 18, wherein the cancer is breast cancer.

20. The method according to claim 19, wherein the breast cancer is metastatic or locally advanced.

21. The method according to claim 18 or 19, wherein the breast cancer is estrogen receptor-positive (ER+) breast cancer.

22. The method according to claim 21, wherein the estrogen receptor-positive (ER+) breast cancer is human epidermal growth factor receptor 2-negative (HER2-).

23. The method according to any one of claims 1 to 22, wherein the subject is a human.

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