Claims for Patent: 12,280,056

Summary for Patent: 12,280,056

Title:	Combination therapy including a KRASG12C inhibitor and one or more additional pharmaceutically active agents for the treatment of cancers
Abstract:	The present invention provides combination therapy that includes an KRASG12C inhibitor, such asor 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 KRASG12C inhibitor and one or more additional pharmaceutically active agents for the treatment of cancers.
Inventor(s):	James Russell LIPFORD, Jude Robert CANON, Anne Y. SAIKI, Karen Louise REX
Assignee:	Amgen Inc
Application Number:	US18/545,932
Patent Claims:	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-enolyl)piperazin-1-yl]pyrido[2,3-d]pyrimidin-2(1H-one, or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of an EGFR inhibitor, 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 EGFR inhibitor is afatinib, erlotinib, lapatinib, cetuximab, or panitumumab. 3. The method of claim 1, wherein the EGFR inhibitor is panitumumab. 4. The method of claim 1, wherein the cancer is colorectal cancer. 5. The method of claim 1, wherein the cancer is non-small cell lung cancer. 6. The method of claim 1, wherein the cancer is pancreatic cancer. 7. The method of claim 3, wherein the cancer is colorectal cancer. 8. The method of claim 3, wherein the cancer is non-small cell lung cancer. 9. The method of claim 3, wherein the cancer is pancreatic cancer. 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, and the EGFR inhibitor are administered simultaneously. 11. 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 EGFR inhibitor are administered separately. 12. The method of claim 4, 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 EGFR inhibitor are administered simultaneously. 13. The method of claim 4, 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 EGFR inhibitor are administered separately. 14. The method of claim 5, 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 EGFR inhibitor are administered simultaneously. 15. The method of claim 5, 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 EGFR inhibitor are administered separately. 16. The method of claim 3, 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 panitumumab are administered simultaneously. 17. The method of claim 3, 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 panitumumab are administered separately. 18. The method of claim 7, 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 panitumumab are administered simultaneously. 19. The method of claim 7, 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 panitumumab are administered separately. 20. The method of claim 8, 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 panitumumab are administered simultaneously. 21. The method of claim 8, wherein 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 panitumumab are administered separately. 22. 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. 23. 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. 24. The method of claim 23, wherein the solid dosage form is a tablet. 25. The method of claim 24, wherein the tablet is administered orally. 26. The method of claim 3, 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. 27. The method of claim 3, 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. 28. The method of claim 27, wherein the solid dosage form is a tablet. 29. The method of claim 28, wherein the tablet is administered orally. 30. 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 panitumumab, wherein the cancer is colorectal cancer, non-small cell lung cancer, or pancreatic cancer. 31. The method of claim 30, wherein the cancer is colorectal cancer. 32. The method of claim 31, 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 panitumumab are administered separately. 33. The method of claim 31, 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 panitumumab are administered simultaneously. 34. The method of claim 31, 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. 35. The method of claim 31, 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. 36. The method of claim 35, wherein the solid dosage form is a tablet. 37. The method of claim 36, wherein the tablet is administered orally.