IP Library › Granted Patent US 12,336,995
Granted Patent B2
US 12,336,995 · App. 17/275,176 · Granted Jun 24, 2025

Combination therapies

Inventors: James Gail Christensen (Carlsbad, CA); Lars Daniel Engstrom (Carlsbad, CA); Ruth Wei Aranda (San Diego, CA); Jill Hallin (San Diego, CA); Peter Olson (San Diego, CA)
Assignee: MIRATI THERAPEUTICS, INC.
A61K31/519A61K31/517A61K31/5377A61K31/5386A61K31/541A61K45/06C07K16/2863
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Quick Facts
Patent No.
US 12,336,995
App. No.
17/275,176
Filed
Mar 10, 2021
Granted
Jun 24, 2025
Kind
B2
Art Unit
1622
USPC
514/210.16
Abstract

The present invention relates to combination therapies for treating KRas G12C cancers. In particular, the present invention relates to methods of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a combination of a pan ErbB family inhibitor and a KRAS G12C inhibitor of Formula (I), Formula (I-A) or Formula (I-B), pharmaceutical compositions comprising a therapeutically effective amounts of the inhibitors, kits comprising the compositions and methods of use therefor.

Claims (39)

1. A method of treating colorectal cancer in a subject in need thereof, comprising administering to the subject a combination therapy, wherein the combination therapy comprises a therapeutically effective amount of cetuximab and a therapeutically effective amount of a KRAS G12C inhibitor of formula:

or a pharmaceutically acceptable salt thereof.

2. The method according to claim 1 , wherein the therapeutically effective amount of the combination of cetuximab and the KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof results in an increased duration of overall survival, an increased duration of progression free survival, an increase in tumor growth regression, an increase in tumor growth inhibition or an increased duration of stable disease in the subject relative to treatment with only the KRas G12C inhibitor.

3. The method according to claim 1 , wherein cetuximab synergistically increases sensitivity of colorectal cancer cells of the colorectal cancer to the KRas G12C inhibitor.

4. The method according to claim 1 , wherein the therapeutically effective amount of the KRas G12C inhibitor is between about 0.01 to 100 mg/kg per day.

5. The method of claim 1 , wherein cetuximab and the KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof are formulated into separate dosage forms.

6. The method of claim 1 , wherein the KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof is administered orally.

7. The method of claim 1 , wherein cetuximab is administered parenterally.

8. The method of claim 1 , wherein cetuximab is administered intravenously.

9. The method of claim 1 , wherein cetuximab is administered prior to the administration of the KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof.

10. The method of claim 1 , wherein cetuximab is administered after the administration of the KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof.

11. The method of claim 1 , wherein the KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof is administered twice per day.

12. The method of claim 1 , wherein cetuximab and the KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof are administered through different administration routes.

13. The method of claim 1 , wherein the KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof is administered as a tablet.

14. A method for inhibiting KRas G12C activity in a colorectal cancer cell, comprising contacting the cell in which inhibition of KRas G12C activity is desired with an effective amount of cetuximab and the KRas G12C inhibitor compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein cetuximab synergistically increases sensitivity of the colorectal cancer cell to the KRas G12C inhibitor.

15. A method for increasing the sensitivity of a colorectal cancer cell to a KRas G12C inhibitor compound comprising administering to a subject with colorectal cancer undergoing KRas Gi 2C treatment with a compound of claim 1 or a pharmaceutically acceptable salt thereof, alone or combined with a pharmaceutically acceptable carrier, excipient or diluents, a therapeutically effective amount of cetuximab, wherein cetuximab synergistically increases the sensitivity of the colorectal cancer cell to the KRas G12C inhibitor.

16. A method of treating colorectal cancer in a subject in need thereof, comprising administering to the subject a combination therapy, wherein the combination therapy comprises a therapeutically effective amount of cetuximab and a therapeutically effective amount of a KRAS G12C inhibitor of formula:

17. The method according to claim 16 , wherein the therapeutically effective amount of the combination of cetuximab and the KRAS G12C inhibitor results in an increased duration of overall survival, an increased duration of progression free survival, an increase in tumor growth regression, an increase in tumor growth inhibition or an increased duration of stable disease in the subject relative to treatment with only the KRas G12C inhibitor.

18. The method according to claim 16 , wherein cetuximab synergistically increases sensitivity of colorectal cancer cells of the colorectal cancer to the KRas G12C inhibitor.

19. The method according to claim 16 , wherein the therapeutically effective amount of the KRas G12C inhibitor is between about 0.01 to 100 mg/kg per day.

20. The method of claim 16 , wherein cetuximab and the KRAS G12C inhibitor are formulated into separate dosage forms.

21. The method of claim 16 , wherein the KRAS G12C inhibitor or a is administered orally.

22. The method of claim 16 , wherein cetuximab is administered parenterally.

23. The method of claim 16 , wherein cetuximab is administered intravenously.

24. The method of claim 16 , wherein cetuximab is administered prior to the administration of the KRAS G12C inhibitor.

25. The method of claim 16 , wherein cetuximab is administered after the administration of the KRAS G12C inhibitor.

26. The method of claim 16 , wherein the KRAS G12C inhibitor is administered twice per day.

27. The method of claim 16 , wherein cetuximab and the KRAS G12C inhibitor are administered through different administration routes.

28. The method of claim 16 , wherein the KRAS G12C inhibitor is administered as a tablet.

29. A method for inhibiting KRas G12C activity in a colorectal cancer cell, comprising contacting the cell in which inhibition of KRas G12C activity is desired with an effective amount of cetuximab and the KRas G12C inhibitor compound according to claim 16 , wherein cetuximab synergistically increases sensitivity of the colorectal cancer cell to the KRas G12C inhibitor.

30. A method for increasing sensitivity of a colorectal cancer cell to a KRas G12C inhibitor compound comprising administering to a subject with colorectal cancer undergoing KRas G12C treatment with the KRAS G12C inhibitor of claim 16 , alone or combined with a pharmaceutically acceptable carrier, excipient or diluents, a therapeutically effective amount of cetuximab, wherein cetuximab synergistically increases the sensitivity of the colorectal cancer cell to the KRas G12C inhibitor.

31. A pharmaceutical composition, comprising a therapeutically effective amount of a combination of cetuximab and the KRas G12C inhibitor according to claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

32. A pharmaceutical composition, comprising a therapeutically effective amount of a combination of cetuximab and the KRas G12C inhibitor according to claim 16 , and a pharmaceutically acceptable excipient.

33. A kit comprising the pharmaceutical composition of claim 31 for treating colorectal cancer in a subject.

34. A kit comprising: a) a pharmaceutical composition comprising cetuximab and b) a pharmaceutical composition comprising a KRas G12C inhibitor of formula:

or a pharmaceutically acceptable salt thereof, for treating colorectal cancer in a subject.

35. A kit comprising the pharmaceutical composition of claim 32 for treating colorectal cancer in a subject.

36. A kit comprising: a) a pharmaceutical composition comprising cetuximab and b) a pharmaceutical composition comprising a KRas G12C inhibitor of formula:

for treating colorectal cancer in a subject.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 13, 2022
From: CHRISTENSEN, JAMES GAIL; ENGSTROM, LARS; ARANDA, RUTH WEI; HALLIN, JILL; OLSON, PETER
To: MIRATI THERAPEUTICS, INC.
Reel/Frame 058637/0882 →
Continuity (2)
Provisional Application 62729189 · Sep 10, 2018
Related Publication 20220054491A1 · Feb 24, 2022
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