Treatment of PD-L1-Positive Melanoma Using an Anti-PD-1 Antibody

Abstract

The invention provides a method of treating a melanoma comprising (i) identifying a patient having a PD-L1 positive melanoma and (ii) administering to the patient an anti-PD-1 antibody or an antigen-binding portion thereof (“an anti-PD-1 antibody monotherapy”). The methods of the invention can extend progression-free survival for over 12 months and/or reduces the tumor size at least about 10%, about 20%, about 30%, about 40%, or about 50% compared to the tumor size prior to the administration.

1 . A method for treating a melanoma tumor in a patient in need thereof comprising:
 (i) identifying a patient having a PD-L1 positive melanoma tumor; and   (ii) administering to the patient an anti-PD-1 antibody or an antigen-binding portion thereof that binds specifically to a human PD-1 (“anti-PD1 antibody monotherapy”), wherein the patient is not administered a combination of an anti-PD-1 antibody or an antigen-binding portion thereof and an anti-CTLA-4 antibody or an antigen-binding portion thereof that binds specifically to a human CTLA-4 (“combination therapy”).   
     
     
         2 . (canceled) 
     
     
         3 . A method for treating a melanoma tumor in a patient in need thereof comprising administering to the patient an anti-PD-1 antibody or an antigen-binding portion thereof that binds specifically to a human PD-1 (“anti-PD-1 antibody monotherapy”), wherein the patient is not administered a combination of an anti-PD-1 antibody or an antigen-binding portion thereof and an anti-CTLA-4 antibody or an antigen-binding portion thereof that binds specifically to a human CTLA-4 (“combination therapy”), wherein the patient is identified as having a PD-L1 positive melanoma tumor prior to the administration. 
     
     
         4 - 8 . (canceled) 
     
     
         9 . The method of  claim 3 , wherein the patient is characterized by (i) extended progression-free survival for over 12 months following the administration, (ii) tumor size reduction at least about 10% compared to the tumor size prior to the administration, or (iii) both (i) and (ii). 
     
     
         10 - 13 . (canceled) 
     
     
         14 . A method for selecting a patient suitable for an anti-PD-1 antibody monotherapy comprising:
 (i) identifying a patient having a PD-L1 positive melanoma tumor; and   (ii) instructing a healthcare provider to administer to the patient an anti-PD-1 antibody monotherapy.   
     
     
         15 . The method of  claim 3 , further comprising measuring a PD-L1 expression on the melanoma tumor. 
     
     
         16 . The method of  claim 3 , wherein the administration treats the melanoma tumor. 
     
     
         17 . The method of  claim 15 , wherein the measuring comprises providing a test tissue sample obtained from the patient, the test tissue sample comprising tumor cells and/or tumor-infiltrating inflammatory cells. 
     
     
         18 . The method of  claim 17 , wherein the measuring further comprises assessing the proportion of cells in the test tissue sample that express PD-L1 on the cell surface. 
     
     
         19 . The method of  claim 18 , wherein the test tissue sample is a formalin-fixed paraffin-embedded (FPPE) tissue sample. 
     
     
         20 . The method of  claim 19 , wherein the presence of PD-L1 is determined using an automated IHC assay. 
     
     
         21 . The method of  claim 20 , wherein the IHC assay is performed using an anti-PD-L1 monoclonal antibody that specifically binds to the PD-L1 and wherein the anti-PD-L1 monoclonal antibody is selected from the group consisting of 28-8, 28-1, 28-12, 29-8, 5H1, and any combination thereof. 
     
     
         22 . The method of  claim 3 , wherein the PD-L1 positive melanoma tumor is characterized by having at least about 5% of tumor cells showing binding to the anti-PD-L1 antibody or an antigen-binding portion thereof. 
     
     
         23 . The method of  claim 3 , wherein the anti-PD-1 antibody or antigen-binding portion thereof cross-competes with nivolumab for binding to human PD-1. 
     
     
         24 . The method of  claim 3 , wherein the anti-PD-1 antibody or antigen-binding portion thereof is a chimeric, humanized or human monoclonal antibody or a portion thereof. 
     
     
         25 . The method of  claim 3 , wherein the anti-PD-1 antibody or antigen-binding portion thereof comprises a heavy chain constant region which is of a human IgG1 or IgG4 isotype. 
     
     
         26 . The method of  claim 3 , wherein the anti-PD-1 antibody is nivolumab. 
     
     
         27 . (canceled) 
     
     
         28 . The method of  claim 3 , wherein the anti-PD-1 antibody or antigen-binding portion thereof is administered at a dose ranging from 0.1 to 10.0 mg/kg body weight once every 2, 3 or 4 weeks. 
     
     
         29 . The method of  claim 28 , wherein the anti-PD-1 antibody or antigen-binding portion thereof is administered at a dose of 1 or 3 mg/kg body weight once every 3 weeks. 
     
     
         30 - 48 . (canceled) 
     
     
         49 . The method of  claim 3 , further comprising administering an anti-cancer agent. 
     
     
         50 . A kit for treating a patient afflicted with a melanoma tumor, the kit comprising:
 (a) a dosage ranging from 0.1 to 10 mg/kg body weight of an anti-PD-1 antibody or an antigen-binding portion thereof; and   (b) instructions for using the anti-PD-1 antibody or the antigen-binding portion thereof in the method of  claim 3 .   
     
     
         51 . (canceled)