Combination therapy containing GDC-6036 and GDC-0077 for the treatment of cancer

Claims

1. Combination therapy containing (a) GDC-6036 or a pharmaceutically acceptable salt thereof; and (b) inavolisib or its pharmaceutically acceptable salt.

2. The combination therapy of claim 1, wherein GDC-6036 is an adipic acid salt thereof.

3. The combination therapy of claim 1 or 2, wherein GDC-6036 or a pharmaceutically acceptable salt thereof is administered once a day in accordance with a dosing regimen comprising one or more cycles.

4. The combination therapy of claim 3, wherein GDC-6036 or a pharmaceutically acceptable salt thereof is administered once daily on days 1-21 of a dosing regimen comprising one or more 21-day cycles, wherein GDC-6036 or a pharmaceutically acceptable salt thereof is administered orally as a tablet or capsule.

5. The combination therapy of claim 3, wherein GDC-6036 or a pharmaceutically acceptable salt thereof is administered once daily in a dosing regimen comprising one or more 28-day cycles, wherein GDC-6036 or a pharmaceutically acceptable salt thereof is administered orally in the form of a tablet or capsule.

6. The combination therapy of any one of claims 1-5, wherein GDC-6036 or a pharmaceutically acceptable salt thereof is administered in an amount of about 50 mg-500 mg.

7. The combination therapy of any one of claims 1-6, wherein GDC-6036 or a pharmaceutically acceptable salt thereof is administered in an amount of about 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, or 800 mg.

8. The combination therapy of any one of claims 1-6, wherein GDC-6036 or a pharmaceutically acceptable salt thereof is administered in an amount of about 100 mg, 200 mg, or 400 mg.

9. The combination therapy of any one of claims 1-6, wherein GDC-6036 or a pharmaceutically acceptable salt thereof is administered in an amount of approximately 200 mg.

10. The combination therapy of any one of claims 1-6, wherein GDC-6036 or a pharmaceutically acceptable salt thereof is administered in an amount of approximately 400 mg.

11. The combination therapy of any one of claims 1-10, wherein inavolisib or a pharmaceutically acceptable salt thereof is administered once daily in a dosing regimen comprising one or more cycles.

12. The combination therapy of claim 11, wherein inavolisib or a pharmaceutically acceptable salt thereof is administered once daily on days 1-21 of a dosing regimen comprising one or more 21-day cycles.

13. The combination therapy of any one of claims 1-12, wherein inavolisib or a pharmaceutically acceptable salt thereof is administered once daily in a dosing regimen comprising one or more 28-day cycles.

14. The combination therapy of any one of claims 1-13, wherein the dosing regimen includes a rest period in which one or both of GDC-6036 and inavolisib are not administered.

15. The combination therapy of any one of claims 1-14, wherein inavolisib is administered in an amount of about 3, 6, or 9 mg.

16. The combination therapy of any one of claims 1-15, wherein inavolisib is administered in an amount of 6 mg.

17. The combination therapy of any one of claims 1-15, wherein inavolisib is administered in an amount of 9 mg.

18. Combination therapy according to any one of claims 1-17 for use in the treatment of lung cancer containing a KRas mutation G12C .

19. The combination therapy of claim 18, wherein the lung cancer is non-small cell lung carcinoma (NSCLC).

20. Combination therapy according to any one of claims 1-17 for use in the treatment of colorectal cancer (CRC) containing a KRas mutation G12C .

21. The combination therapy of any one of claims 1-20, wherein the patient is assessed for the presence of the KRasG12C mutation prior to administration.

22. Combination therapy according to any one of claims 1-21, wherein the presence of mutant PIK3CA is not assessed before administration.

23. A method for treating lung cancer mediated by KRas mutation G12C , in a patient having such type of lung cancer, wherein the method comprises administering an effective amount of a combination therapy comprising: (a) GDC-6036 or a pharmaceutically acceptable salt thereof, administered once daily in accordance with a dosing regimen comprising one or more cycles; and (b) inavolisib or its pharmaceutically acceptable salt, administered once daily in accordance with a dosing regimen that includes one or more cycles.

24. The method according to claim 23, wherein the lung cancer is NSCLC.

25. The method according to claim 23 or 24, wherein the lung cancer is adenocarcinoma, squamous cell carcinoma of the lung, or large cell carcinoma of the lung.

26. A method for treating a solid tumor containing a KRasG12C mutation in a patient having such cancer, said method comprising administering an effective amount of a combination therapy comprising: (a) GDC-6036 or a pharmaceutically acceptable salt thereof, administered once daily in accordance with a dosing regimen comprising one or more cycles; and (b) inavolisib or its pharmaceutically acceptable salt, administered once daily in accordance with a dosing regimen that includes one or more cycles.

27. The method according to claim 26, wherein the solid tumor is colorectal cancer (CRC).

28. The method according to any one of paragraphs 23-27, further comprising (a) determining the absence or presence of the KRasG12C mutation in a sample taken from a patient with a suspected diagnosis of cancer; (b) administering to the patient a combination therapy as described herein comprising an effective amount of GDC-6036 or a pharmaceutically acceptable salt thereof and inavolisib.

29. A method for treating a tissue-agnostic cancer containing a KRasG12C mutation in a patient having such cancer, said method comprising administering an effective amount of a combination therapy comprising (i) determining the absence or presence of the KRasG12C mutation in a sample taken from a patient with a suspected diagnosis of cancer; (ii) if the patient sample contains the KRasG12C mutation, administering an effective amount of a combination therapy containing (a) GDC-6036 or its pharmaceutically acceptable salt, administered once daily in accordance with a dosing regimen that includes one or more cycles; (b) inavolisib or its pharmaceutically acceptable salt, administered once daily in accordance with a dosing regimen that includes one or more cycles.

30. The method according to any one of claims 23-29, wherein the dosing regimen comprises one or more 21-day cycles.

31. The method of claim 30, wherein the dosing regimen includes a rest period in which one or both of GDC-6036 and inavolisib are not administered.

32. The method according to any one of paragraphs 23-29, wherein the dosing regimen comprises one or more 28-day cycles.

33. The method according to any one of claims 23-32, wherein GDC-6036 is an adipic acid salt thereof.

34. The method according to any one of claims 23-33, wherein GDC-6036 or a pharmaceutically acceptable salt thereof is administered orally in the form of a tablet or capsule.

35. The method according to any one of claims 23-34, wherein GDC-6036 or a pharmaceutically acceptable salt thereof is administered in an amount of about 50 mg-500 mg.

36. The method according to any one of paragraphs 23-35, wherein GDC-6036 or a pharmaceutically acceptable salt thereof is administered in an amount of about 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg or 800 mg.

37. The method of any one of claims 23-36, wherein GDC-6036 or a pharmaceutically acceptable salt thereof is administered in an amount of about 100 mg, 200 mg, or 400 mg.

38. The method according to any one of claims 23-37, wherein GDC-6036 or a pharmaceutically acceptable salt thereof is administered in an amount of about 200 mg.

39. The method according to any one of claims 23-37, wherein GDC-6036 or a pharmaceutically acceptable salt thereof is administered in an amount of about 400 mg.

40. The method according to any one of claims 23-39, wherein inavolisib is administered in an amount of about 3 mg, 6 mg, or 9 mg.

41. The method according to any one of claims 23-40, wherein inavolisib is administered in an amount of 6 mg.

42. The method according to any one of claims 23-40, wherein inavolisib is administered in an amount of 9 mg.

43. The method of any one of claims 23-42, wherein the patient is not assessed for the presence of mutant PIK3CA prior to administration.

44. Use of combination therapy comprising GDC-6036 or a pharmaceutically acceptable salt thereof and inavolisib or a pharmaceutically acceptable salt thereof for the treatment of lung cancer, colorectal cancer, or pancreatic cancer, as described herein.

45. The use according to claim 44, wherein the cancer is lung cancer or colorectal cancer, and further comprises a dosing regimen comprising: (i) administering GDC-6036 or a pharmaceutically acceptable salt thereof once a day in accordance with a dosing regimen comprising one or more cycles; and (ii) administering inavolisib once a day in accordance with a dosing regimen comprising one or more cycles.

46. ​​Use of a combination therapy comprising GDC-6036 or a pharmaceutically acceptable salt thereof and inavolisib or a pharmaceutically acceptable salt thereof for the manufacture of a medicinal product for the treatment of lung cancer, colorectal cancer or pancreatic cancer.

47. The use according to claim 46, wherein the cancer is lung cancer or colorectal cancer, and further comprises a dosing regimen comprising: (i) administering GDC-6036 or a pharmaceutically acceptable salt thereof once a day in accordance with a dosing regimen comprising one or more cycles; and (ii) administering inavolisib once a day in accordance with a dosing regimen comprising one or more cycles.

48. The use according to claim 46, wherein the cancer is colorectal cancer, and further comprising a dosing regimen comprising: (i) administering GDC-6036 or a pharmaceutically acceptable salt thereof once daily in accordance with a dosing regimen comprising one or more 21-day cycles; and (ii) administering inavolisib in accordance with a dosing regimen comprising one or more 21-day cycles.

49. The use according to any one of paragraphs 44-48, wherein the dosing regimen comprises one or more 21-day cycles.

50. The use according to any one of paragraphs 44-48, wherein the dosing regimen comprises one or more 28-day cycles.