Method of treating cancer using immune checkpoint inhibitor

Abstract

This disclosure provides a method for treating HPV-positive squamous cell carcinoma of the head and neck comprising administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody or an anti-PD-L1 antibody. The disclosure also provides a method for treating HPV-negative squamous cell carcinoma of the head and neck administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody or an anti-PD-L1 antibody. The subject can be additionally administered another anti-cancer agent.

1 . A method for treating a subject afflicted with a tumor derived from a human papilloma virus (HPV)-positive squamous cell carcinoma head and neck cancer (SCCHN) comprising administering to the subject a flat dose of about 240 mg of nivolumab once every two weeks without regard for the weight of the subject. 
     
     
         2 . A method of treating a subject afflicted with a tumor derived from an HPV-positive SCCHN comprising:
 (i) measuring a level of HPV in a sample of the subject, wherein the subject is positive for HPV; and   (ii) administering to the subject a flat dose of about 240 mg of nivolumab once every two weeks without regard for the weight of the subject.   
     
     
         3 - 4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein the HPV-positive SCCHN comprises a tumor expressing one or more proteins derived from an HPV or comprising a nucleotide sequence encoding the one or more proteins. 
     
     
         6 . (canceled) 
     
     
         7 . The method of  claim 5 , wherein the one or more proteins derived from an HPV comprise p16, Ki-67, Cyclin D1, p53, ProEx C, E6, E7, or any combination thereof. 
     
     
         8 - 10 . (canceled) 
     
     
         11 . The method of  claim 1 , wherein the HPV comprises HPV subtype 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, or any combination thereof. 
     
     
         12 . The method of  claim 1 , wherein more than about 70% of tumor cells in the tumor show strong and diffuse nuclear and cytoplasmic staining by an immunohistochemistry against p16. 
     
     
         13 . (canceled) 
     
     
         14 . The method of  claim 1 , wherein the tumor further expresses PD-L1. 
     
     
         15 - 31 . (canceled) 
     
     
         32 . The method of  claim 1 , wherein the subject exhibits an overall survival of at least about 10 months after the administration. 
     
     
         33 - 34 . (canceled) 
     
     
         35 . The method of  claim 1 , which further comprises administering one or more additional anti-cancer agents. 
     
     
         36 . The method of  claim 35 , wherein at least one of the anti-cancer agents is selected from the group consisting of (i) an antibody or antigen-binding portion thereof that binds specifically to a CTLA-4 and inhibits CTLA-4 activity, (ii) a chemotherapy, (iii) a platinum-based doublet chemotherapy, (iv) a tyrosine kinase inhibitor, (v) an anti-VEGF inhibitor, and (vi) any combination thereof. 
     
     
         37 . (canceled) 
     
     
         38 . A kit for treating a human subject afflicted with a tumor derived from an HPV-positive SCCHN, the kit comprising:
 (a) a dose of about 240 mg of nivolumab; and   (b) instructions for determining the HPV positivity of the tumor and, if the tumor is positive for HPV, administering the nivolumab to the subject in the method of  claim 1 .   
     
     
         39 - 80 . (canceled) 
     
     
         81 . The method of  claim 1 , wherein the subject received one or more anti-cancer agents prior to the administration of the nivolumab. 
     
     
         82 . The method of  claim 81 , wherein the one or more anti-cancer agents were not effective in treating the tumor. 
     
     
         83 . The method of  claim 82 , wherein the one or more anti-cancer agents comprise a platinum-based therapy. 
     
     
         84 . The method of  claim 2 , wherein the subject exhibits an overall survival of at least about 10 months after the administration. 
     
     
         85 . The method of  claim 2 , wherein the HPV-positive SCCHN comprises a tumor expressing one or more proteins derived from an HPV or comprising a nucleotide sequence encoding the one or more proteins. 
     
     
         86 . The method of  claim 85 , wherein the one or more proteins derived from an HPV comprise p16, Ki-67, Cyclin D1, p53, ProEx C, E6, E7, or any combination thereof. 
     
     
         87 . The method of  claim 2 , wherein the HPV comprises HPV subtype 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, or any combination thereof. 
     
     
         88 . The method of  claim 2 , wherein more than about 70% of tumor cells in the tumor show strong and diffuse nuclear and cytoplasmic staining by an immunohistochemistry against p16. 
     
     
         89 . The method of  claim 2 , wherein the tumor further expresses PD-L1.