IP Library › Granted Patent US 12,582,657
Granted Patent B2
US 12,582,657 · App. 18/545,953 · Granted Mar 24, 2026

Combination therapy including a KRAS G12C inhibitor and one or more additional pharmaceutically active agents for the treatment of cancers

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 12,582,657
App. No.
18/545,953
Granted
Mar 24, 2026
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 human subject in need thereof, the method comprising administering to the human subject a therapeutically effective amount of 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-(1M)-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-4-[(2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl]pyrido[2,3-d]pyrimidin-2(1H)-one, or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of carboplatin, wherein the cancer is non-small cell lung cancer, small intestine cancer, appendix cancer, colorectal cancer, endometrial cancer, pancreatic cancer, skin cancer, gastric cancer, nasal cavity cancer, or bile duct cancer.

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

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

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

5 . The method of claim 1 , wherein the 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-(1M)-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-4-[(2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl]pyrido[2,3-d]pyrimidin-2(1H)-one, or the pharmaceutically acceptable salt thereof, and the carboplatin are administered simultaneously.

6 . The method of claim 1 , wherein the 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-(1M)-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-4-[(2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl]pyrido[2,3-d]pyrimidin-2(1H)-one, or the pharmaceutically acceptable salt thereof, and the carboplatin are administered separately.

7 . The method of claim 2 , wherein the 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-(1M)-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-4-[(2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl]pyrido[2,3-d]pyrimidin-2(1H)-one, or the pharmaceutically acceptable salt thereof, and the carboplatin are administered simultaneously.

8 . The method of claim 2 , wherein the 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-(1M)-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-4-[(2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl]pyrido[2,3-d]pyrimidin-2(1H)-one, or the pharmaceutically acceptable salt thereof, and the carboplatin are administered separately.

9 . The method of claim 1 , wherein the 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-(1M)-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-4-[(2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl]pyrido[2,3-d]pyrimidin-2(1H)-one, or the pharmaceutically acceptable salt thereof, is administered to an adult.

10 . The method of claim 1 , wherein the 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-(1M)-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-4-[(2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl]pyrido[2,3-d]pyrimidin-2(1H)-one, or the pharmaceutically acceptable salt thereof, is administered as a solid dosage form.

11 . The method of claim 10 , wherein the solid dosage form is a tablet.

12 . The method of claim 11 , wherein the tablet is administered orally.

13 . The method of claim 2 , wherein the 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-(1M)-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-4-[(2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl]pyrido[2,3-d]pyrimidin-2(1H)-one, or the pharmaceutically acceptable salt thereof, is administered to an adult.

14 . The method of claim 2 , wherein the 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-(1M)-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-4-[(2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl]pyrido[2,3-d]pyrimidin-2(1H)-one, or the pharmaceutically acceptable salt thereof, is administered as a solid dosage form.

15 . The method of claim 14 , wherein the solid dosage form is a tablet.

16 . The method of claim 15 , wherein the tablet is administered orally.

17 . A method of treating cancer mediated by a KRAS G12C mutation in a human subject in need thereof, the method comprising administering to the human subject a therapeutically effective amount of 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-(1M)-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-4-[(2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl]pyrido[2,3-d]pyrimidin-2(1H)-one and a therapeutically effective amount of carboplatin, wherein the cancer is colorectal cancer, non-small cell lung cancer, or pancreatic cancer.

18 . The method of claim 17 , wherein the cancer is non-small cell lung cancer.

19 . The method of claim 18 , wherein the 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-(1M)-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-4-[(2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl]pyrido[2,3-d]pyrimidin-2(1H)-one and the carboplatin are administered separately.

20 . The method of claim 18 , wherein the 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-(1M)-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-4-[(2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl]pyrido[2,3-d]pyrimidin-2(1H)-one and the carboplatin are administered simultaneously.

21 . The method of claim 18 , wherein the 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-(1M)-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-4-[(2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl]pyrido[2,3-d]pyrimidin-2(1H)-one is administered to an adult.

22 . The method of claim 18 , wherein the 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-(1M)-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-4-[(2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl]pyrido[2,3-d]pyrimidin-2(1H)-one is administered as a solid dosage form.

23 . The method of claim 22 , wherein the solid dosage form is a tablet.

24 . The method of claim 23 , wherein the tablet is administered orally.

25 . The method of claim 17 , wherein the 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-(1M)-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-4-[(2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl]pyrido[2,3-d]pyrimidin-2(1H)-one and the carboplatin are administered separately.

26 . The method of claim 17 , wherein the 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-(1M)-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-4-[(2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl]pyrido[2,3-d]pyrimidin-2(1H)-one and the carboplatin are administered simultaneously.

27 . The method of claim 17 , wherein the 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-(1M)-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-4-[(2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl]pyrido[2,3-d]pyrimidin-2(1H)-one is administered to an adult.

28 . The method of claim 17 , wherein the 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-(1M)-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-4-[(2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl]pyrido[2,3-d]pyrimidin-2(1H)-one is administered as a solid dosage form.

29 . The method of claim 28 , wherein the solid dosage form is a tablet.

30 . The method of claim 29 , wherein the tablet is administered orally.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 3, 2024
From: LIPFORD, JAMES RUSSELL; CANON, JUDE ROBERT; SAIKI, ANNE Y.
To: AMGEN INC.
Reel/Frame 066994/0620 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 3, 2024
From: LIPFORD, JAMES RUSSELL; CANON, JUDE ROBERT; SAIKI, ANNE Y.; REX, KAREN LOUISE
To: AMGEN INC.
Reel/Frame 066994/0628 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 3, 2024
From: LIPFORD, JAMES RUSSELL; CANON, JUDE ROBERT; SAIKI, ANNE Y.; REX, KAREN LOUISE
To: AMGEN INC.
Reel/Frame 066994/0637 →
Continuity (6)
Continuation 17870573 · Jul 21, 2022
Continuation 16687563 · Nov 18, 2019
Provisional Application 62865819 · Jun 24, 2019
Provisional Application 62821376 · Mar 20, 2019
Provisional Application 62769355 · Nov 19, 2018
Related Publication 20240173328A1 · May 30, 2024
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