Methods of treating cancer using PD-1 axis binding antagonists and MEK inhibitors

Patent metadata

Field	Value
Publication number	US-9724413-B2
Application number	US-201214236064-A
Country	US
Kind code	B2
Filing date	Aug 1, 2012
Priority date	Aug 1, 2011
Publication date	Aug 8, 2017
Grant date	Aug 8, 2017

Abstract

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.

First claim

What is claimed is:

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-L1 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-L1 antibody inhibits the binding of PD-L1 to PD-1.

3. The method of claim 1 , wherein the anti-PD-L1 antibody inhibits the binding of PD-L1 to B7-1.

4. The method of claim 1 , wherein the anti-PD-L1 antibody inhibits the binding of PD-L1 to both PD-1 and B7-1.

5. The method of claim 1 , wherein the anti-PD-L1 antibody is selected from the group consisting of: YW243.55.S70, MPDL3280A, and MDX-1105.

6. The method of claim 1 , wherein the anti-PD-L1 antibody comprises a heavy chain comprising HVR-H1 sequence of SEQ ID NO:15, HVR-H2 sequence of SEQ ID NO:16, and HVR-H3 sequence of SEQ ID NO:3; and a light chain comprising HVR-L1 sequence of SEQ ID NO:17, HVR-L2 sequence of SEQ ID NO:18, and HVR-L3 sequence of SEQ ID NO:19.

7. The method of claim 1 , wherein the anti-PD-L1 antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:24 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:21.

8. The method of claim 1 , wherein the MEK inhibitor is G02443714, G02442104 or G00039805.

9. The method of claim 1 , wherein the cancer contains a BRAF V600E mutation.

10. The method of claim 1 , wherein the cancer 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-L1 antibody.

17. The method of claim 1 , wherein the MEK inhibitor is administered simultaneous with the anti-PD-L1 antibody.

18. The method of claim 1 , wherein the MEK inhibitor is administered after the anti-PD-L1 antibody.

19. The method of claim 1 , wherein the anti-PD-L1 antibody is a monoclonal antibody.

20. The method of claim 1 , wherein the anti-PD-L1 antibody is a humanized antibody.

21. The method of claim 1 , wherein the anti-PD-L1 antibody is a human antibody.

22. The method of claim 1 , wherein the anti-PD-L1 antibody is administered intravenously, intramuscularly, subcutaneously, topically, orally, transdermally, intraperitoneally, intraorbitally, by implantation, by inhalation, intrathecally, intraventricularly, or intranasally.

23. A method for treating or delaying progression of colorectal cancer in an individual comprising administering to the individual an effective amount of GDC-0973, or a pharmaceutically acceptable salt thereof, and an effective amount of an anti-PD-L1 antibody, wherein the anti-PD-L1 antibody comprises a heavy chain comprising an HVR-H1 sequence of SEQ ID NO:15, an HVR-H2 sequence of SEQ ID NO:16, and an HVR-H3 sequence of SEQ ID NO:3; and a light chain comprising an HVR-L1 sequence of SEQ ID NO:17;, an HVR-L2 sequence of SEQ ID NO:18, and an HVR-L3 sequence of SEQ ID NO:19.

24. The method of claim 23 , wherein the heavy chain comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:24 and the light chain comprises a light chain variable domain comprising the amino acid sequence of SEQ ID NO:21.

25. The method of claim 23 , wherein the anti-PDL1 antibody is MPDL3280A.

26. A method for treating or delaying progression of melanoma in an individual comprising administering to the individual an effective amount of GDC-0973, or a pharmaceutically acceptable salt thereof, and an effective amount of an anti-PD-L1 antibody, wherein the melanoma is BRAF wildtype, and wherein the anti-PD-L1 antibody comprises a heavy chain comprising an HVR-H1 sequence of SEQ ID NO:15, an HVR-H2 sequence of SEQ ID NO:16, and an HVR-H3 sequence of SEQ ID NO:3; and a light chain comprising an HVR-L1 sequence of SEQ ID NO:17, an HVR-L2 sequence of SEQ ID NO:18, and an HVR-L3 sequence of SEQ ID NO:19.

27. The method of claim 26 , wherein the heavy chain comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:24 and the light chain comprises a light chain variable domain comprising the amino acid sequence of SEQ ID NO:21.

28. The method of claim 26 , wherein the anti-PDL1 antibody is MPDL 3280A.

29. The method of claim 1 , wherein the MEK inhibitor is s G02442104, or a pharmaceutically acceptable salt or solvate thereof.

30. The method of claim 1 , wherein the MEK inhibitor is G-38963, or a pharmaceutically acceptable salt or solvate thereof.

31. The method of claim 1 , wherein the MEK inhibitor is G02443714, or a pharmaceutically acceptable salt or solvate thereof.

32. The method of claim 1 , wherein the MEK inhibitor is G00039805, or a pharmaceutically acceptable salt or solvate thereof.

33. The method of claim 1 , wherein the MEK inhibitor is GDC-0973, or a pharmaceutically acceptable salt or solvate thereof.

Assignees

• Maecker Heather
• Irving Bryan
• Genentech Inc

Inventors

• Maecker Heather
• Irving Bryan

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61K47/64

  Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65) · CPC title