Combination therapy for treating cancer

Abstract

The present invention relates to compositions comprising inhibitors of human histone methyltransferase EZH2 and one or more other therapeutic agents, particularly anticancer agents such as prednisone, and methods of combination therapy for administering to subjects in need thereof for the treatment of cancer.

1 .- 27 . (canceled) 
     
     
         28 . A method for treating a lymphoma selected from non-Hodgkin's lymphoma, diffuse large B-cell lymphoma, and follicular lymphoma in a subject in need thereof comprising administering to the subject:
 (a) a Compound 44 having the following formula:   
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof; and
 (b) ABT-199. 
 
     
     
         29 . The method of  claim 28 , wherein the lymphoma is non-Hodgkin's lymphoma. 
     
     
         30 . The method of  claim 28 , wherein the lymphoma is diffuse large B-cell lymphoma. 
     
     
         31 . The method of  claim 28 , wherein the lymphoma is follicular lymphoma. 
     
     
         32 . The method of  claim 29 , wherein the non-Hodgkin's lymphoma is an EZH2 wild type non-Hodgkin's lymphoma. 
     
     
         33 . The method of  claim 29 , wherein the non-Hodgkin's lymphoma is an EZH2 mutant non-Hodgkin's lymphoma. 
     
     
         34 . The method of  claim 33 , wherein the EZH2 mutant non-Hodgkin's lymphoma has an Y646, A682 or A692 mutation. 
     
     
         35 . The method of  claim 29 , wherein the non-Hodgkin's lymphoma is EZH2 inhibitor resistant or recurrent following remission on the most recent therapy. 
     
     
         36 . The method of  claim 30 , wherein the diffuse large B-cell lymphoma is an EZH2 wild type diffuse large B-cell lymphoma. 
     
     
         37 . The method of  claim 30 , wherein the diffuse large B-cell lymphoma is an EZH2 mutant diffuse large B-cell lymphoma. 
     
     
         38 . The method of  claim 37 , wherein the EZH2 mutant diffuse large B-cell lymphoma has an Y646, A682 or A692 mutation. 
     
     
         39 . The method of  claim 30 , wherein the diffuse large B-cell lymphoma is EZH2 inhibitor resistant or recurrent following remission on the most recent therapy. 
     
     
         40 . The method of  claim 31 , wherein the follicular lymphoma is an EZH2 wild type follicular lymphoma. 
     
     
         41 . The method of  claim 31 , wherein the follicular lymphoma is an EZH2 mutant follicular lymphoma. 
     
     
         42 . The method of  claim 41 , wherein the EZH2 mutant follicular lymphoma has an Y646, A682 or A692 mutation. 
     
     
         43 . The method of  claim 31 , wherein the follicular lymphoma is EZH2 inhibitor resistant or recurrent following remission on the most recent therapy.