Combination of hdac inhibitor and anti-pd-1 antibody for treatment of cancer

Abstract

Described herein are methods for the treatment of cancer in a subject. In particular, methods are provided for the treatment of non small cell lung cancer and melanoma with a combination of entinostat and an anti-PD-1 or an anti-PD-L1 antibody.

1 .- 15 . (canceled) 
     
     
         16 . A method of treating cancer, wherein the method comprises, administering to a patient a combination comprising entinostat, and an anti PD-1 or an anti-PD-L1 antibody, and wherein the entinostat, and the anti-PD-1 or the anti-PD-L1 antibody are administered sequentially in either order or simultaneously. 
     
     
         17 . The method of  claim 16 , wherein entinostat and the anti-PD-1 or the anti-PD-L1 antibody are administered sequentially in either order or simultaneously during a treatment cycle of 21 days. 
     
     
         18 .- 19 . (canceled) 
     
     
         20 . The method of  claim 17 , wherein the anti-PD-1 antibody is administered on day 1 of the treatment cycle. 
     
     
         21 . The method of  claim 17 , wherein the anti-PD-1 antibody is administered at a dose of 2 mg/kg. 
     
     
         22 . The method of  claim 17 , wherein the anti-PD-1 antibody is administered at a fixed dose of 200 mg. 
     
     
         23 . The method of  claim 16 , wherein the entinostat is administered at a dose of 3 mg/kg. 
     
     
         24 . The method of  claim 16 , wherein the entinostat is administered at a dose of 5 mg/kg. 
     
     
         25 . The method of  claim 16 , wherein the entinostat is administered at a dose of 10 mg/kg. 
     
     
         26 . The method of  claim 16 , wherein the entinostat is administered weekly. 
     
     
         27 . The method of  claim 16 , wherein the anti-PD-1 antibody or the anti-PD-L1 antibody is administered every two weeks. 
     
     
         28 .- 31 . (canceled) 
     
     
         32 . A method of selecting a patient for a combination therapy comprising administering entinostat, and an anti-PD-1 or an anti-PD-L1 antibody, the method comprising measuring PD-L1 expression in a tumor tissue sample obtained from the patient. 
     
     
         33 . The method of  claim 32 , further comprising administering to the patient the combination therapy comprising entinostat, and an anti-PD-1 or an anti-PD-L1 antibody if tumor proportion score (TPS) for PD-L1 expression is greater than or equal to 50%. 
     
     
         34 . The method of  claim 32 , further comprising administering to the patient the combination therapy comprising entinostat, and an anti-PD-1 or an anti-PD-L1 antibody if tumor proportion score (TPS) for PD-L1 expression is greater than or equal to 1%. 
     
     
         35 . The method of  claim 32 , further comprising administering to the patient the combination therapy comprising entinostat, and an anti-PD-1 or an anti-PD-L1 antibody if tumor proportion score (TPS) for PD-L1 expression is greater than or equal to 49%. 
     
     
         36 . The method of  claim 32 , further comprising administering to the patient the combination therapy comprising entinostat, and an anti-PD-1 or an anti-PD-L1 antibody if tumor proportion score (TPS) for PD-L1 expression is between 1% and 50%. 
     
     
         37 . The method of  claim 32 , wherein the tumor tissue sample is from a squamous or nonsqaumos non small cell lung cancer. 
     
     
         38 . The method of  claim 32 , wherein the tumor tissue sample is from a melanoma. 
     
     
         39 . The method of  claim 32 , wherein the anti PD-1 antibody is pembrolizumab. 
     
     
         40 . The method of  claim 32 , wherein the patient received at least one prior therapy. 
     
     
         41 . The method of  claim 32 , wherein the patient has progressed on a prior therapy with an anti-CTLA4 antibody or a BRAF inhibitor.