Methods of treating cancer using PD-1 axis binding antagonists and MEK inhibitors
The present invention describes combination treatment comprising a PD-1 axis binding antagonist and a MEK inhibitor and methods for use thereof, including methods of treating conditions where enhanced immunogenicity is desired such as increasing tumor immunogenicity for the treatment of cancer.
1. A method for treating or delaying progression of colorectal cancer or melanoma in an individual comprising administering to the individual an effective amount of an anti-PD-1 antibody and a MEK inhibitor, wherein the MEK inhibitor is selected from the group consisting of G02442104, G-38963, G02443714, G00039805 and GDC-0973, or a pharmaceutically acceptable salt or solvate thereof.
2. The method of claim 1 , wherein the anti-PD-1 antibody inhibits the binding of PD-1 to its ligand binding partners.
3. The method of claim 2 , wherein the anti-PD-1 antibody inhibits the binding of PD-1 to PD-L1.
4. The method of claim 2 , wherein the anti-PD-1 antibody inhibits the binding of PD-1 to PD-L2.
5. The method of claim 2 wherein the anti-PD-1 antibody inhibits the binding of PD-1 to both PD-L1 and PD-L2.
6. The method of claim 1 , wherein the anti-PD-1 antibody is MDX-1106.
7. The method of claim 1 , wherein the anti-PD-1 antibody is Merck 3745.
8. The method of claim 1 , wherein the MEK inhibitor is G02443714, G02442104 or G00039805, or a pharmaceutically acceptable salt or solvate thereof.
9. The method of claim 1 , wherein the colorectal cancer or melanoma contains a BRAF V600E mutation.
10. The method of claim 1 , wherein the colorectal cancer or melanoma contains a BRAF wildtype.
11. The method of claim 1 , wherein the colorectal cancer contains a KRAS wildtype.
12. The method of claim 1 , wherein the colorectal cancer contains an activating KRAS mutation.
13. The method of claim 1 , wherein the treatment results in a sustained response in the individual after cessation of the treatment.
14. The method of claim 1 , wherein the MEK inhibitor is administered continuously.
15. The method of claim 1 , wherein the MEK inhibitor is administered intermittently.
16. The method of claim 1 , wherein the MEK inhibitor is administered before the anti-PD-1 antibody.
17. The method of claim 1 , wherein the MEK inhibitor is administered simultaneous with the anti-PD-1 antibody.
18. The method of claim 1 , wherein the MEK inhibitor is administered after the anti-PD-1 antibody.
19. The method of claim 1 , wherein the anti-PD-1 antibody is administered intravenously, intramuscularly, subcutaneously, topically, orally, transdermally, intraperitoneally, intraorbitally, by implantation, by inhalation, intrathecally, intraventricularly, or intranasally.
20. The method of claim 1 , wherein the MEK inhibitor is G02442104, or a pharmaceutically acceptable salt or solvate thereof.
21. The method of claim 1 , wherein the MEK inhibitor is G-38963, or a pharmaceutically acceptable salt or solvate thereof.
22. The method of claim 1 , wherein the MEK inhibitor is G02443714, or a pharmaceutically acceptable salt or solvate thereof.
23. The method of claim 1 , wherein the MEK inhibitor is G00039805, or a pharmaceutically acceptable salt or solvate thereof.
24. The method of claim 1 , wherein the MEK inhibitor is GDC-0973, or a pharmaceutically acceptable salt or solvate thereof.
25. The method of claim 1 , wherein the method is for treating or delaying progression of colorectal cancer in the individual, and the MEK inhibitor is GDC-0973 or a pharmaceutically acceptable salt or solvate thereof.
26. The method of claim 25 , wherein the anti-PD-1 antibody is MDX-1106.
27. The method of claim 25 , wherein the anti-PD-1 antibody is Merck 3745.
28. The method of claim 1 , wherein the method is for treating or delaying progression of melanoma in the individual, and the MEK inhibitor is GDC-0973 or a pharmaceutically acceptable salt or solvate thereof.
29. The method of claim 28 , wherein the anti-PD-1 antibody is MDX-1106.
30. The method of claim 28 , wherein the anti-PD-1 antibody is Merck 3745.