Methods of treating cancer using pd-1 axis binding antagonists and tigit inhibitors

Abstract

The present invention describes combination treatment comprising a PD-1 axis binding antagonist and an agent that decreases or inhibits TIGIT expression and/or activity 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 or chronic infection.

1 .- 166 . (canceled) 
     
     
         167 . A method of treating cancer in a human subject in need thereof, comprising administering to the human subject an effective amount of:
 a. an anti-PD-1 antagonistic antibody; and   b. an anti-TIGIT antagonistic antibody.   
     
     
         168 . The method of  claim 167 , wherein the anti-TIGIT antagonistic antibody is a human antibody or a humanized antibody. 
     
     
         169 . The method of  claim 167 , wherein the anti-TIGIT antagonistic antibody is a monoclonal antibody. 
     
     
         170 . The method of  claim 167 , wherein the anti-TIGIT antagonistic antibody is a monoclonal humanized antibody. 
     
     
         171 . The method of  claim 167 , wherein the anti-TIGIT antagonistic antibody is a monoclonal human antibody. 
     
     
         172 . The method of  claim 167 , wherein the anti-TIGIT antagonistic antibody is an IgG antibody. 
     
     
         173 . The method of  claim 172 , wherein the anti-TIGIT antagonistic antibody is an IgG-1 antibody. 
     
     
         174 . The method of  claim 173 , wherein the anti-TIGIT antagonistic antibody is a monoclonal human IgG-1 antibody or a monoclonal humanized IgG-1 antibody. 
     
     
         175 . The method of  claim 172 , wherein the anti-TIGIT antagonistic antibody is an IgG-4 antibody. 
     
     
         176 . The method of  claim 175 , wherein the anti-TIGIT antagonistic antibody is a monoclonal human IgG-4 antibody or a monoclonal humanized IgG-4 antibody. 
     
     
         177 . The method of  claim 167 , wherein the anti-PD-1 antagonistic antibody is nivolumab (MDX-1106). 
     
     
         178 . The method of  claim 167 , wherein the anti-PD-1 antagonistic antibody is lambrolizumab (MK-3475). 
     
     
         179 . The method of  claim 167 , wherein the anti-PD-1 antagonistic antibody is a human antibody or a humanized antibody. 
     
     
         180 . The method of  claim 167 , wherein the anti-PD-1 antagonistic antibody is a monoclonal antibody. 
     
     
         181 . The method of  claim 167 , wherein the anti-PD-1 antagonistic antibody is a monoclonal humanized antibody. 
     
     
         182 . The method of  claim 167 , wherein the anti-PD-1 antagonistic antibody is a monoclonal human antibody. 
     
     
         183 . The method of  claim 167 , wherein the anti-PD-1 antagonistic antibody is an IgG antibody. 
     
     
         184 . The method of  claim 183 , wherein the anti-PD-1 antagonistic antibody is an IgG-1 antibody. 
     
     
         185 . The method of  claim 184 , wherein the anti-PD-1 antagonistic antibody is a monoclonal human IgG-1 antibody or a monoclonal humanized IgG-1 antibody. 
     
     
         186 . The method of  claim 183 , wherein the anti-PD-1 antagonistic antibody is an IgG-4 antibody. 
     
     
         187 . The method of  claim 186 , wherein the anti-PD-1 antagonistic antibody is a monoclonal human IgG-4 antibody or a monoclonal humanized IgG-4 antibody. 
     
     
         188 . The method of  claim 167 , further comprising administering an effective amount of at least one chemotherapeutic agent. 
     
     
         189 . The method of  claim 167 , wherein the cancer is selected from the group consisting of a non-small cell lung cancer, a small cell lung cancer, a renal cell cancer, a colorectal cancer, an ovarian cancer, a breast cancer, a pancreatic cancer, a gastric carcinoma, a bladder cancer, an esophageal cancer, a mesothelioma, a melanoma, a head and neck cancer, a thyroid cancer, a sarcoma, a prostate cancer, a glioblastoma, a cervical cancer, a thymic carcinoma, a leukemia, a lymphoma, a myeloma, a mycosis fungoides, a Merkel cell cancer, and a hematologic malignancy. 
     
     
         190 . The method of  claim 167 , wherein the cancer is selected from the group consisting of a non-small cell lung cancer, a small cell lung cancer, a hepatocellular cancer, a renal cell cancer, a head and neck cancer, a colorectal cancer, a breast cancer, an esophageal cancer, a gastric carcinoma, a cervical cancer, an endometrial cancer, a bladder cancer, a melanoma, a lymphoma, and a Merkel cell cancer. 
     
     
         191 . The method of  claim 167 , wherein the cancer is melanoma. 
     
     
         192 . The method of  claim 167 , wherein the cancer is non-small cell lung cancer. 
     
     
         193 . The method of  claim 167 , wherein the cancer is a solid tumor. 
     
     
         194 . The method of  claim 167 , wherein the cancer is a hematologic malignancy. 
     
     
         195 . The method of  claim 167 , wherein the anti-TIGIT antagonistic antibody is administered before or after the anti-PD-1 antagonistic antibody. 
     
     
         196 . The method of  claim 167 , wherein the anti-TIGIT antagonistic antibody is administered simultaneously with the anti-PD-1 antagonistic antibody.