Combination therapy for treatment of cancer

Patent metadata

Field	Value
Publication number	US-11364222-B2
Application number	US-201916460502-A
Country	US
Kind code	B2
Filing date	Jul 2, 2019
Priority date	Jan 6, 2017
Publication date	Jun 21, 2022
Grant date	Jun 21, 2022

Abstract

Compositions, combinations and methods comprising a CDK4/6 inhibitor of Formula D with a selective estrogen receptor downregulator of Formula A, B or C that are advantageous for the treatment of abnormal cellular proliferation, including a cancer or a tumor.

First claim

We claim:

1. A method of treating an estrogen-related cancer or tumor in a human comprising administering to the human in need thereof a therapeutically effective amount of a SERD in combination with a therapeutically effective amount of a CDK4/6 inhibitor, wherein the SERD is selected from:

or a pharmaceutically acceptable salt thereof,
and wherein the CDK4/6 inhibitor is selected from:

or a pharmaceutically acceptable salt thereof; wherein the estrogen-related cancer or tumor is breast cancer, ovarian cancer, endometrial cancer, kidney cancer, uterine cancer, prostate cancer, or lung cancer.

2. The method of claim 1 , wherein the estrogen-related cancer is metastatic endocrine therapy resistant breast cancer.

3. The method of claim 1 , wherein the cancer is breast cancer.

4. The method of claim 3 , wherein the breast cancer is hormone receptor positive metastatic breast cancer.

5. The method of claim 3 , wherein the breast cancer is a tamoxifen resistant breast cancer.

6. The method of claim 3 , wherein the breast cancer is a triple negative breast cancer.

7. The method of claim 1 , wherein the human is further administered another chemotherapeutic agent in combination or alternation with the SERD and the CDK4/6 inhibitor.

8. The method of claim 1 , wherein the SERD is

or a pharmaceutically acceptable salt thereof.

9. The method of claim 1 , wherein the SERD is

or a pharmaceutically acceptable salt thereof.

10. The method of claim 1 , wherein the SERD is

or a pharmaceutically acceptable salt thereof.

11. The method of claim 1 , wherein the CDK4/6 inhibitor is

or a pharmaceutically acceptable salt thereof.

12. The method of claim 1 , wherein the CDK4/6 inhibitor is

or a pharmaceutically acceptable salt thereof.

13. The method of claim 1 , wherein the CDK4/6 inhibitor is

or a pharmaceutically acceptable salt thereof.

14. The method of claim 1 , wherein the CDK4/6 inhibitor is

or a pharmaceutically acceptable salt thereof.

15. The method of claim 1 , wherein the SERD is

or a pharmaceutically acceptable salt thereof,
and the CDK4/6 inhibitor is

or a pharmaceutically acceptable salt thereof.

16. The method of claim 1 , wherein the CDK4/6 inhibitor is

or a pharmaceutically acceptable salt thereof.

17. The method of claim 16 , wherein the SERD is

or a pharmaceutically acceptable salt thereof.

18. The method of claim 17 , wherein the estrogen-related cancer is metastatic endocrine therapy resistant breast cancer.

19. The method of claim 17 , wherein the cancer is breast cancer.

20. The method of claim 19 , wherein the breast cancer is hormone receptor positive metastatic breast cancer.

21. The method of claim 19 , wherein the breast cancer is a tamoxifen resistant breast cancer.

22. The method of claim 17 , wherein the human is further administered another chemotherapeutic agent in combination or alternation with the SERD and the CDK4/6 inhibitor.

23. A pharmaceutical composition comprising a SERD, a CDK4/6 inhibitor, and a pharmaceutically acceptable carrier, wherein the SERD is selected from:

or a pharmaceutically acceptable salt thereof,
and wherein the CDK4/6 inhibitor is selected from:

or a pharmaceutically acceptable salt thereof.

24. The pharmaceutical composition of claim 23 , wherein the SERD is

or a pharmaceutically acceptable salt thereof.

25. The pharmaceutical composition of claim 23 , wherein the SERD is

or a pharmaceutically acceptable salt thereof.

26. The pharmaceutical composition of claim 23 , wherein the SERD is

or a pharmaceutically acceptable salt thereof.

27. The pharmaceutical composition of claim 23 , wherein the SERD is

or a pharmaceutically acceptable salt thereof.

28. The pharmaceutical composition of claim 23 , wherein the CDK4/6 inhibitor is

or a pharmaceutically acceptable salt thereof.

29. The pharmaceutical composition of claim 23 , wherein the CDK4/6 inhibitor is

or a pharmaceutically acceptable salt thereof.

30. The pharmaceutical composition of claim 23 , wherein the CDK4/6 inhibitor is

or a pharmaceutically acceptable salt thereof.

31. A pharmaceutical composition comprising:
(i) a compound of structure:

or a pharmaceutically acceptable salt thereof;
(ii) a compound of structure:

or a pharmaceutically acceptable salt thereof; and
(iii) a pharmaceutically acceptable carrier.

32. A combination comprising a therapeutically effective amount of a SERD and a CDK4/6 inhibitor;
wherein the SERD is selected from:

or a pharmaceutically acceptable salt thereof,
and wherein the CDK4/6 in

Assignees

• G1 Therapeutics Inc
• Univ Illinois

Inventors

• Strum Jay C
• Thatcher Gregory R
• Xiong Rui
• Zhao Jiong
• Tonetti Debra A

Classifications

• 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

• A61K45/06

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

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title