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

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.

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.S70, 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; 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. 
     
     
         53 . The method of  claim 50 , 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. 
     
     
         54 . The method of  claim 38 , wherein the PD-1 axis binding antagonist is a PD-L2 binding antagonist. 
     
     
         55 . The method of  claim 54 , wherein the PD-L2 binding antagonist is an antibody. 
     
     
         56 . The method of  claim 54 , wherein the PD-L2 binding antagonist is an immunoadhesin. 
     
     
         57 . The method of any one of  claims 32 - 56 , wherein the cancer is lung cancer, bladder cancer, breast cancer, renal cell carcinoma, melanoma, colorectal cancer, or a heme malignancy. 
     
     
         58 . The method of  claim 57 , wherein the lung cancer is non-small cell lung cancer (NSCLC). 
     
     
         59 . The method of any one of  claims 32 - 58 , wherein the cancer cells in the individual express PD-L1. 
     
     
         60 . The method of any one of  claims 32 - 59 , wherein the taxane is nab-paclitaxel (ABRAXANE®), paclitaxel, or docetaxel. 
     
     
         61 . The method of  claim 60 , wherein the taxane is nab-paclitaxel (ABRAXANE®). 
     
     
         62 . The method of  claim 60 , wherein the taxane is paclitaxel. 
     
     
         63 . The method of any one of  claims 1 - 62 , wherein the PD-1 axis binding antagonist and/or the taxane are administered intravenously, intramuscularly, subcutaneously, topically, orally, transdermally, intraperitoneally, intraorbitally, by implantation, by inhalation, intrathecally, intraventricularly, or intranasally. 
     
     
         64 . The method of any one of  claims 1 - 63 , further comprising administering an effective amount of a chemotherapeutic agent. 
     
     
         65 . The method of  claim 64 , wherein the chemotherapeutic agent is a platinum-based chemotherapeutic agent. 
     
     
         66 . The method of  claim 65 , wherein the platinum-based chemotherapeutic agent is carboplatin. 
     
     
         67 . Use of a human PD-1 axis binding antagonist in the manufacture of a medicament for treating or delaying progression of cancer in an individual, wherein the medicament comprises the human PD-1 axis binding antagonist and an optional pharmaceutically acceptable carrier, and wherein the treatment comprises administration of the medicament in combination with a composition comprising a taxane and an optional pharmaceutically acceptable carrier. 
     
     
         68 . Use of a taxane in the manufacture of a medicament for treating or delaying progression of cancer in an individual, wherein the medicament comprises the taxane and an optional pharmaceutically acceptable carrier, and wherein the treatment comprises administration of the medicament in combination with a composition comprising a human PD-1 axis binding antagonist and an optional pharmaceutically acceptable carrier. 
     
     
         69 . A composition comprising a human PD-1 axis binding antagonist and an optional pharmaceutically acceptable carrier for use in treating or delaying progression of cancer in an individual, wherein the treatment comprises administration of said composition in combination with a second composition, wherein the second composition comprises a taxane and an optional pharmaceutically acceptable carrier. 
     
     
         70 . A composition comprising a taxane and an optional pharmaceutically acceptable carrier for use in treating or delaying progression of cancer in an individual, wherein the treatment comprises administration of said composition in combination with a second composition, wherein the second composition comprises a human PD-1 axis binding antagonist and an optional pharmaceutically acceptable carrier. 
     
     
         71 . 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 a taxane and an optional pharmaceutically acceptable carrier for treating or delaying progression of cancer in an individual. 
     
     
         72 . A kit comprising a first medicament comprising a PD-1 axis binding antagonist and an optional pharmaceutically acceptable carrier, and a second medicament comprising a taxane and an optional pharmaceutically acceptable carrier. 
     
     
         73 . The kit of  claim 72 , 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. 
     
     
         74 . A kit comprising a medicament comprising a taxane 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.