Use of anti-pd-1 antibody in combination with anti-cd27 antibody in cancer treatment

Abstract

This invention provides methods for treating cancer in a subject comprising administering to the subject an anti-PD-1 antibody and an anti-CD27 antibody. In some embodiments, the cancer is colorectal cancer, rectal cancer, colon cancer, lung cancer, melanoma, ovarian cancer, head and neck cancer, or any combination thereof.

What is claimed is: 
     
         1 . A method for treating a subject afflicted with a tumor comprising administering the subject in need thereof
 an antibody or an antigen-binding portion thereof that binds specifically to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity (“anti-PD-1 antibody or antigen-binding portion thereof”) in combination with   an antibody or an antigen-binding portion thereof that specifically binds to CD27 (“anti-CD27 antibody or antigen-binding portion thereof”).   
     
     
         2 . The method of  claim 1 , wherein the tumor is colorectal cancer, rectal cancer, colon cancer, lung cancer, melanoma, ovarian cancer, head and neck cancer, or any combination thereof. 
     
     
         3 . The method of  claim 2 , wherein the lung cancer is non-small cell lung cancer (NSCLC). 
     
     
         4 . The method of  claim 1 , wherein the anti-PD-1 antibody or antigen-binding portion thereof cross-competes with nivolumab for binding to human PD-1. 
     
     
         5 . The method of  claim 1 , wherein the anti-CD27 antibody or antigen-binding portion thereof cross-competes with varlilumab for binding to human CD27. 
     
     
         6 . The method of  claim 1 , wherein:
 (i) the anti-PD-1 antibody is nivolumab;   (ii) the anti-CD27 antibody is varlilumab; or   (iii) the anti-PD-1 antibody is nivolumab and the anti-CD27 antibody is varlilumab.   
     
     
         7 . The method of  claim 1 , wherein the anti-PD-1 antibody or antigen-binding portion thereof is administered at a dose ranging from at least about 0.1 mg/kg to at least about 10.0 mg/kg body weight once about every 1, 2 or 3 weeks. 
     
     
         8 . The method of  claim 7 , wherein the anti-PD-1 antibody or antigen-binding portion thereof is administered at a dose of at least about 3 mg/kg body weight once about every 2 weeks. 
     
     
         9 . The method of  claim 1 , wherein the anti-CD27 antibody or antigen-binding portion thereof is administered at a dose ranging from at least about 0.01 mg/kg to at least about 10 mg/kg body weight once about every 1, 2 or 3 weeks. 
     
     
         10 . The method of  claim 9 , wherein the anti-CD27 antibody or antigen-binding fragment thereof is administered at a dose of 0.1 mg/kg body weight, 1 mg/kg body weight, or 10 mg/kg body weight once about every 2 weeks. 
     
     
         11 . The method of  claim 1 , wherein the anti-PD-1 antibody or antigen-binding fragment thereof and the anti-CD27 antibody or antigen-binding fragment thereof are formulated for intravenous administration. 
     
     
         12 . The method of  claim 1 , wherein the anti-PD-1 antibody or antigen-binding fragment thereof and the anti-CD27 antibody or antigen-binding fragment thereof are administered sequentially, concurrently in separate compositions, or concurrently as a single composition. 
     
     
         13 . The method of  claim 1 , wherein:
 (i) the anti-PD-1 antibody or antigen-binding portion thereof is administered at a subtherapeutic dose;   (ii) the anti-CD27 antibody or antigen-binding portion thereof is administered at a subtherapeutic dose; or   (iii) the anti-PD-1 antibody or antigen-binding portion thereof and the anti-CD27 antibody or antigen-binding portion thereof are each administered at a subtherapeutic dose.   
     
     
         14 . The method of  claim 1 , wherein the tumor is colon cancer. 
     
     
         15 . The method of  claim 14 , further comprising determining the microsatellite status of the subject's tumor. 
     
     
         16 . The method of  claim 14 , wherein the subject has a microsatellite instability low (MSI-L) tumor or a microsatellite stable (MSS) tumor. 
     
     
         17 . The method of  claim 15 , wherein the microsatellite status of the subject's tumor is determined prior to treatment with the anti-PD-1 antibody or antigen-binding portion thereof in combination with the anti-CD27 antibody or antigen-binding portion thereof. 
     
     
         18 . The method of  claim 1 , wherein the tumor is PD-L1 positive. 
     
     
         19 . The method of  claim 1 , further comprising measuring PD-L1 expression in the tumor. 
     
     
         20 . The method of  claim 1 , further comprising administering an anti-cancer agent.