Methods of treating cancers using pd-1 axis binding antagonists and taxanes

Patent metadata

Field	Value
Publication number	US-2016257752-A1
Application number	US-201615167125-A
Country	US
Kind code	A1
Filing date	May 27, 2016
Priority date	Dec 17, 2013
Publication date	Sep 8, 2016
Grant date	—

Abstract

The invention provides methods and compositions for treating cancer and for enhancing immune function in an individual having cancer. The methods comprise administering a PD-1 axis binding antagonist and a taxane.

First claim

What is claimed is:

1 . A method for treating or delaying progression of cancer in an individual comprising administering to the individual an effective amount of a human PD-1 axis binding antagonist and a taxane.

2 . The method of claim 1 , wherein the PD-1 axis binding antagonist is selected from the group consisting of a PD-1 binding antagonist, a PD-L1 binding antagonist, and a PD-L2 binding antagonist.

3 . The method of claim 2 , wherein the PD-1 axis binding antagonist is a PD-1 binding antagonist.

4 . The method of claim 3 , wherein the PD-1 binding antagonist inhibits the binding of PD-1 to its ligand binding partners.

5 . The method of claim 4 , wherein the PD-1 binding antagonist inhibits the binding of PD-1 to PD-L1.

6 . The method of claim 4 , wherein the PD-1 binding antagonist inhibits the binding of PD-1 to PD-L2.

7 . The method of claim 4 , wherein the PD-1 binding antagonist inhibits the binding of PD-1 to both PD-L1 and PD-L2.

8 . The method of any one of claims 4 - 7 , wherein the PD-1 binding antagonist is an antibody.

9 . The method of claim 4 , wherein the PD-1 binding antagonist is selected from the group consisting of MDX-1106 (nivolumab), MK-3475 (lambrolizumab), CT-011 (pidilizumab), and AMP-224.

10 . The method of claim 2 , wherein the PD-1 axis binding antagonist is a PD-L1 binding antagonist.

11 . The method of claim 10 , wherein the PD-L1 binding antagonist inhibits the binding of PD-L1 to PD-1.

12 . The method of claim 10 , wherein the PD-L1 binding antagonist inhibits the binding of PD-L1 to B7-1.

13 . The method of claim 10 , wherein the PD-L1 binding antagonist inhibits the binding of PD-L1 to both PD-1 and B7-1.

14 . The method of any one of claims 11 - 13 , wherein the PD-L1 binding antagonist is an antibody.

15 . The method of claim 14 , wherein the antibody is selected from the group consisting of: YW243.55.570, MPDL3280A, MDX-1105, and MED14736.

16 . The method of claim 14 , wherein the antibody comprises a heavy chain comprising HVR-H1 sequence of SEQ ID NO:19, HVR-H2 sequence of SEQ ID NO:20, and HVR-H3 sequence of SEQ ID NO:21; and a light chain comprising HVR-L1 sequence of SEQ ID NO:22, HVR-L2 sequence of SEQ ID NO:23, and HVR-L3 sequence of SEQ ID NO:24.

17 . The method of claim 14 , wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:26 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:4.

18 . The method of claim 2 , wherein the PD-1 axis binding antagonist is a PD-L2 binding antagonist.

19 . The method of claim 18 , wherein the PD-L2 binding antagonist is an antibody.

20 . The method of claim 18 , wherein the PD-L2 binding antagonist is an immunoadhesin.

21 . The method of any one of claims 1 - 20 , wherein the cancer is lung cancer, bladder cancer, breast cancer, renal cell carcinoma, melanoma, colorectal cancer, or a heme malignancy.

22 . The method of claim 21 , wherein the lung cancer is non-small cell lung cancer (NSCLC).

23 . The method of any one of claims 1 - 22 , wherein the individual has cancer or has been diagnosed with cancer.

24 . The method of claim 23 , wherein the cancer cells in the individual express PD-L1.

25 . The method of any one of claims 1 - 24 , wherein the treatment results in a response in the individual.

26 . The method of claim 25 , wherein the response is a complete response.

27 . The method of claim 25 or claim 26 , wherein the response is a sustained response after cessation of the treatment.

28 . The method of any one of claims 1 - 27 , wherein the taxane is administered before the PD-1 axis binding antagonist, simultaneous with the PD-1 axis binding antagonist, or after the PD-1 axis binding antagonist.

29 . The method of any one of claims 1 - 28 , wherein the taxane is nab-paclitaxel (ABRAXANE®), paclitaxel, or docetaxel.

30 . The method of claim 29 , wherein the taxane is nab-paclitaxel (ABRAXANE®).

31 . The method of claim 29 , wherein the taxane is paclitaxel.

32 . A method of enhancing immune function in an individual having cancer comprising administering an effective amount of a PD-1 axis binding antagonist and a taxane.

33 . The method of claim 32 , wherein CD8+ T cells in the individual have enhanced priming, activation, proliferation and/or cytolytic activity relative to prior to the administration of the PD-1 axis binding antagonist and the taxane.

34 . The method of claim 32 , wherein the number of CD8+ T cells is elevated relative to prior to administration of the combination.

35 . The method of claim 34 , wherein the CD8+ T cell is an antigen-specific CD8+ T cell.

36 . The method of claim 32 , wherein Treg function is suppressed relative to prior to the administration of the combination.

37 . The method of claim 32 , wherein T cell exhaustion is decreased relative to prior to the administration of the combination.

38 . The method of any one of claims 32 - 37 , wherein the PD-1 axis binding antagonist is selected from the group consisting of a PD-1 binding antagonist, a PD-L1 binding antagonist and a PD-L2 binding antagonist.

39 . The method of claim 38 , wherein the PD-1 axis binding antagonist is a PD-1 binding antagonist.

40 . The method of claim 39 , wherein the PD-1 binding antagonist inhibits the binding of PD-1 to its ligand binding partners.

41 . The method of claim 40 , wherein the PD-1 binding antagonist inhibits the binding of PD-1 to PD-L1.

42 . The method of claim 40 , wherein the PD-1 binding antagonist inhibits the binding of PD-1 to PD-L2.

43 . The method of claim 40 , wherein the PD-1 binding antagonist inhibits the binding of PD-1 to both PD-L1 and PD-L2.

44 . The method of any one of claims 40 - 43 , wherein the PD-1 binding antagonist is an antibody.

45 . The method of claim 40 , wherein the PD-1 binding antagonist is selected from the group consisting of MDX-1106 (nivolumab), MK-3475 (lambrolizumab), CT-011 (pidilizumab), and AMP-224.

46 . The method of claim 38 , wherein the PD-1 axis binding antagonist is a PD-L1 binding antagonist.

47 . The method of claim 46 , wherein the PD-L1 binding antagonist inhibits the binding of PD-L1 to PD-1.

48 . The method of claim 46 , wherein the PD-L1 binding antagonist inhibits the binding of PD-L1 to B7-1.

49 . The method of claim 46 , wherein the PD-L1 binding antagonist inhibits the binding of PD-L1 to both PD-1 and B7-1.

50 . The method of any one of claims 46 - 49 , wherein the PD-L1 binding antagonist is an antibody.

51 . The method of claim 50 , wherein antibody is selected from the group consisting of: YW243.55.570, MPDL3280A, MDX-1105, and MED14736.

52 . The method of claim 50 , wherein the antibody comprises a heavy chain comprising HVR-H1 sequence of SEQ ID NO:19, HVR-H2 sequence of SEQ ID NO:20, and HVR-H3 sequence of SEQ ID NO:21; a

Assignees

• Genentech Inc

Inventors

• Kim Jeong
• Cheung Jeanne

Classifications

• A61K39/39558 Primary

  against tumor tissues, cells, antigens · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P43/00

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