COMBINATION THERAPY COMPRISING OX40 BINDING AGONISTS AND PD-1 AXIS BINDING ANTAGONISTS

• US 20160166685A1
• Filed: 11/16/2015
• Published: 06/16/2016
• Est. Priority Date: 11/17/2014
• Status: Abandoned Application

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Cheung, Jeanne, HUSENI, Mahrukh, Kim, Jeong
• Application Number:
  US14/942,896
• Publication Number:
  US 20160166685A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 2039/55 characterised by the host/recipient, e.g. newborn with maternal antibodies
• CPC Class Codes: A61K 38/16 Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof enzyme inhibitors A61K38/005
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/2827 against B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C07K 16/2878 against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
• CPC Class Codes: C07K 2317/75 Agonist effect on antigen
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

The invention provides compositions and methods for treating cancers. The method comprises administering a PD-1 axis binding antagonist and an OX40 binding agonist.

Claims

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 an OX40 binding agonist, wherein the individual has cancer or has been diagnosed with cancer, and wherein the cancer cells in a tumor sample of the cancer from the individual do not express PD-L1.

2. (canceled)

3. (canceled)

4. 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 an OX40 binding agonist, wherein the individual has cancer or has been diagnosed with cancer, and wherein the cancer cells in a tumor sample of the cancer from the individual express PD-L1.

6. The method of claim 4, wherein the PD-L1 biomarker is detected in between 0% and 1% of the sample.

7. The method of claim 4, wherein the PD-L1 biomarker is detected in between 0% and 5% of the sample.

11. The method of claim 4, wherein the sample has an IHC score of IHC 0 or IHC 1.

12. The method of claim 4, wherein the individual has cancer that is resistant to a PD-1 axis binding antagonist.

13. The method of claim 4, wherein the individual is refractory to a PD-1 axis binding antagonist.

14. The method of claim 4, wherein the PD-1 axis binding antagonist is selected from the group consisting of a PD-1 binding antagonist, a PDL1 binding antagonist and a PDL2 binding antagonist.

20. The method of claim 14, wherein the PD-1 binding antagonist is an antibody.

21. The method of claim 14, wherein the PD-1 binding antagonist is nivolumab, pembrolizumab, CT-011, or AMP-224.

29. The method of claim 14, wherein the PDL1 binding antagonist is an anti-PDL1 antibody.

30. The method of claim 29, wherein the anti-PDL1 antibody is a monoclonal antibody.

33. The method of claim 29, wherein the PDL1 binding antagonist is selected from the group consisting of:

YW243.55.S70, MPDL3280A, MDX-1105, and MEDI4736.

34. The method of claim 29, wherein the antibody comprises a heavy chain comprising HVR-H1 sequence of GFTFSDSWIH (SEQ ID NO:

1), HVR-H2 sequence of AWISPYGGSTYYADSVKG (SEQ ID NO;

2), and HVR-H3 sequence of RHWPGGFDY (SEQ ID NO;

3); and

a light chain comprising HVR-L1 sequence of RASQDVSTAVA (SEQ ID NO;

4), HVR-L2 sequence of SASFLYS (SEQ ID NO;

5), and HVR-L3 sequence of QQYLYHPAT (SEQ ID NO;

6).

35. The method of claim 29, wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of EVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVAWISPYGGSTYY ADS VKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARRHWPGGFDYWGQGTLVTVSS (SEQ ID NO:

7) or EVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVAWI SPYGGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARRHWPGGFDYWGQ GTLVTVSSASTK (SEQ ID NO;

8) and a light chain variable region comprising the amino acid sequence of DIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIY SASF LYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTKVEIKR (SEQ ID NO;

9).

36. The method of claim 14, wherein the PD-1 axis binding antagonist is a PDL2 binding antagonist.

40. The method of claim 4, wherein the OX40 binding agonist is selected from the group consisting of an OX40 agonist antibody that binds human OX40, an OX40L agonist fragment comprising one or more extracellular domains of OX40L, an OX40 oligomeric receptor, and an OX40 immunoadhesin.

42. The method of claim 40, wherein the OX40 agonist antibody is MEDI6469, MEDI0562, or MEDI6383.

43. The method of claim 40, wherein the OX40 agonist antibody is a full-length human IgG1 antibody.

44. The method of claim 40, wherein the OX40 binding agonist is a trimeric OX40L-Fc protein.

46. The method of claim 4, wherein the cancer is breast cancer, lung cancer, ovarian cancer, gastric cancer, bladder cancer, pancreatic cancer, endometrial cancer, colon cancer, kidney cancer, esophageal cancer, prostate cancer, colorectal cancer, glioblastoma, neuroblastoma, or hepatocellular carcinoma.

47. The method of claim 4, wherein the treatment results in a sustained response in the individual after cessation of the treatment.

48. The method of claim 4, wherein the OX40 binding agonist 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.

110. The method of claim 4, further comprising administering a chemotherapeutic agent for treating or delaying progression of cancer.

5. (canceled)

8-10. -10. (canceled)

15-19. -19. (canceled)

22-28. -28. (canceled)

31. (canceled)

32. (canceled)

37-39. -39. (canceled)

41. (canceled)

45. (canceled)

49. (canceled)

50. A method of enhancing immune function in an individual having cancer comprising administering an effective amount of a PD-1 axis binding antagonist and an OX40 binding agonist, wherein the individual has been diagnosed with cancer, and wherein the cancer cells in a tumor sample of the cancer from the individual do not express PD-L1.

51. (canceled)

52. (canceled)

53. A method of enhancing immune function in an individual having cancer comprising administering an effective amount of a PD-1 axis binding antagonist and an OX40 binding agonist, wherein the individual has been diagnosed with cancer, and wherein the cancer cells in a tumor sample of the cancer from the individual express PD-L1.

54-109. -109. (canceled)

111-119. -119. (canceled)

120. A kit comprising a medicament comprising a PD-1 axis binding antagonist and an optional pharmaceutically acceptable carrier, and a package insert comprising instructions for administration of the medicament in combination with a composition comprising an OX40 binding agonist and an optional pharmaceutically acceptable carrier for treating or delaying progression of cancer in an individual, wherein cells in a tumor sample of the cancer from the individual express PD-L1.

121. (canceled)

122. A kit comprising a first medicament comprising a PD-1 axis binding antagonist and an optional pharmaceutically acceptable carrier, and a second medicament comprising an OX40 binding agonist and an optional pharmaceutically acceptable carrier, wherein the kit further comprises a package insert comprising instructions for administration of the first medicament and the second medicament for treating or delaying progression of cancer in an individual, wherein cells in a tumor sample of the cancer from the individual express PD-L1.

123. (canceled)

124. A kit comprising a medicament comprising an OX40 binding agonist and an optional pharmaceutically acceptable carrier, and a package insert comprising instructions for administration of the medicament in combination with a composition comprising a PD-1 axis binding antagonist and an optional pharmaceutically acceptable carrier for treating or delaying progression of cancer in an individual, wherein cells in a tumor sample of the cancer from the individual express PD-L1.