IP Library › Granted Patent US 11,439,645
Granted Patent B2
US 11,439,645 · App. 16/687,563 · Granted Sep 13, 2022

Combination therapy including a KRAS

Inventors: James Russell Lipford (Thousand Oaks, CA); Jude Robert Canon (Newbury Park, CA); Anne Y. Saiki (Moorpark, CA); Karen Louise Rex (Thousand Oaks, CA)
Assignee: Amgen Inc.
A61K31/519A61P35/00A61K31/555C07K16/2818
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Quick Facts
Patent No.
US 11,439,645
App. No.
16/687,563
Granted
Sep 13, 2022
Kind
B2
Abstract

The present invention provides combination therapy that includes an KRAS G12C inhibitor, such as or a pharmaceutically acceptable salt thereof, and one or more additional pharmaceutically active agents, particularly for the treatment of cancers. The invention also relates to pharmaceutical compositions that contain an KRAS G12C inhibitor and one or more additional pharmaceutically active agents for the treatment of cancers.

Claims (30)

1. A method of treating cancer mediated by a KRAS G12C mutation in a patient, the method comprising administering to the patient a therapeutically effective amount of (1M)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(2-propanyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(2-propenoyl)-1-piperazinyl)pyrido[2,3-d]pyrimidin-2(1H)-one, or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of an AKT inhibitor, wherein the cancer is non-small cell lung cancer, colorectal cancer, pancreatic cancer, appendix cancer, endometrial cancer, esophageal cancer, gastric cancer, small intestine cancer, nasal cavity cancer, paranasal sinus cancer, bile duct cancer, skin cancer, or intraocular melanoma.

2. The method of claim 1 , wherein the AKT inhibitor is AZD5363.

3. The method of claim 1 , wherein the cancer is non-small cell lung cancer.

4. The method of claim 1 , wherein the cancer is pancreatic cancer.

5. The method of claim 1 , wherein the cancer is colorectal cancer.

6. The method of claim 2 , wherein the cancer is non-small cell lung cancer.

7. The method of claim 2 , wherein the cancer is pancreatic cancer.

8. The method of claim 2 , wherein the cancer is colorectal cancer.

9. The method of claim 1 , wherein (1M)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(2-propanyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(2-propenoyl)-1-piperazinyl)pyrido[2,3-d]pyrimidin-2(1H)-one and the AKT inhibitor are administered simultaneously.

10. The method of claim 1 , wherein (1M)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(2-propanyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(2-propenoyl)-1-piperazinyl)pyrido[2,3-d]pyrimidin-2(1H)-one and the AKT inhibitor are administered separately.

11. The method of claim 3 , wherein (1M)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(2-propanyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(2-propenoyl)-1-piperazinyl)pyrido[2,3-d]pyrimidin-2(1H)-one and the AKT inhibitor are administered simultaneously.

12. The method of claim 3 , wherein (1M)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(2-propanyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(2-propenoyl)-1-piperazinyl)pyrido[2,3-d]pyrimidin-2(1H)-one and the AKT inhibitor are administered separately.

13. The method of claim 4 , wherein (1M)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(2-propanyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(2-propenoyl)-1-piperazinyl)pyrido[2,3-d]pyrimidin-2(1H)-one and the AKT inhibitor are administered simultaneously.

14. The method of claim 4 , wherein (1M)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(2-propanyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(2-propenoyl)-1-piperazinyl)pyrido[2,3-d]pyrimidin-2(1H)-one and the AKT inhibitor are administered separately.

15. The method of claim 5 , wherein (1M)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(2-propanyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(2-propenoyl)-1-piperazinyl)pyrido[2,3-d]pyrimidin-2(1H)-one and the AKT inhibitor are administered simultaneously.

16. The method of claim 5 , wherein (1M)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(2-propanyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(2-propenoyl)-1-piperazinyl)pyrido[2,3-d]pyrimidin-2(1H)-one and the AKT inhibitor are administered separately.

17. The method of claim 2 , wherein (1M)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(2-propanyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(2-propenoyl)-1-piperazinyl)pyrido[2,3-d]pyrimidin-2(1H)-one and AZD5363 are administered simultaneously.

18. The method of claim 6 , wherein (1M)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(2-propanyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(2-propenoyl)-1-piperazinyl)pyrido[2,3-d]pyrimidin-2(1H)-one and AZD5363 are administered separately.

19. The method of claim 7 , wherein (1M)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(2-propanyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(2-propenoyl)-1-piperazinyl)pyrido[2,3-d]pyrimidin-2(1H)-one and AZD5363 are administered simultaneously.

20. The method of claim 7 , wherein (1M)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(2-propanyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(2-propenoyl)-1-piperazinyl)pyrido[2,3-d]pyrimidin-2(1H)-one and AZD5363 are administered separately.

21. The method of claim 8 , wherein (1M)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(2-propanyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(2-propenoyl)-1-piperazinyl)pyrido[2,3-d]pyrimidin-2(1H)-one and AZD5363 are administered simultaneously.

22. The method of claim 8 , wherein (1M)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(2-propanyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(2-propenoyl)-1-piperazinyl)pyrido[2,3-d]pyrimidin-2(1H)-one and AZD5363 are administered separately.

23. The method of claim 1 , wherein (1M)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(2-propanyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(2-propenoyl)-1-piperazinyl)pyrido[2,3-d]pyrimidin-2(1H)-one is administered as a solid dosage form.

24. The method of claim 2 , wherein AZD5363 is administered as a solid dosage form.

25. The method of claim 23 , wherein the solid dosage form is a tablet.

26. The method of claim 24 , wherein the solid dosage form is a tablet.

27. The method of claim 25 , wherein the tablet is administered orally.

28. The method of claim 26 , wherein the tablet is administered orally.

29. The method od claim 2 , wherein (1M)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(2-propanyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(2-propenoyl)-1-piperazinyl)pyrido[2,3-d]pyrimidin-2(1H)-one and AZD5363 are administered separately.

30. The method od claim 6 , wherein (1M)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(2-propanyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(2-propenoyl)-1-piperazinyl)pyrido[2,3-d]pyrimidin-2(1H)-one and AZD5363 are administered simultaneously.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 23, 2020
From: LIPFORD, JAMES RUSSELL; CANON, JUDE ROBERT; SAIKI, ANNE Y.
To: AMGEN INC.
Reel/Frame 053017/0780 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 23, 2020
From: LIPFORD, JAMES RUSSELL; CANON, JUDE ROBERT; SAIKI, ANNE Y.; REX, KAREN LOUISE
To: AMGEN INC.
Reel/Frame 053018/0097 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 23, 2020
From: LIPFORD, JAMES RUSSELL; CANON, JUDE ROBERT; SAIKI, ANNE Y.; REX, KAREN LOUISE
To: AMGEN INC.
Reel/Frame 053018/0337 →
Continuity (4)
Provisional Application 62865819 · Jun 24, 2019
Provisional Application 62821376 · Mar 20, 2019
Provisional Application 62769355 · Nov 19, 2018
Related Publication 20200222407A1 · Jul 16, 2020
Cited By (7)
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