Ezh2 inhibitors for treating lymphoma

Abstract

The present invention relates to compositions comprising inhibitors of human histone methyltransferase EZH2 and their use for the treatment of cancer.

1 . A method for treating non-Hodgkin's lymphoma (NHL) comprising administering a therapeutically effective amount of an EZH2 inhibitor to a subject in need thereof, wherein the NHL is selected from diffuse large B-cell lymphoma (DLBCL), a germinal center-derived lymphoma, a non-germinal center-derived lymphoma, follicular lymphoma (FL), primary mediastinal large B-cell lymphoma (PMBCL), marginal zone lymphoma (MZL), Burkitt's lymphoma and other non-Hodgkin's lymphoma subtype. 
     
     
         2 . The method of  claim 1 , wherein the NHL is DLBCL. 
     
     
         3 . The method of  claim 1 , wherein the NHL is a germinal center-derived lymphoma. 
     
     
         4 . The method of  claim 1 , wherein the NHL is non-germinal center-derived lymphoma. 
     
     
         5 . The method of  claim 1 , wherein the NHL is follicular lymphoma. 
     
     
         6 . The method of  claim 1 , wherein the NHL is PMBCL. 
     
     
         7 . The method of  claim 1 , wherein the NHL is marginal zone lymphoma. 
     
     
         8 . The method of  claim 1 , wherein the NHL is Burkitt's lymphoma. 
     
     
         9 . The method of  claim 1 , wherein the NHL is other Non-Hodgkin's lymphoma subtype. 
     
     
         10 . The method of  claim 1 , wherein the NHL is an EZH2 wild type B-cell lymphoma. 
     
     
         11 . The method of  claim 1 , wherein the NHL is an EZH2 mutant B-cell lymphoma. 
     
     
         12 . The method of  claim 1 , wherein the EZH2 inhibitor is administered orally. 
     
     
         13 . The method of  claim 1 , wherein the subject is a human being. 
     
     
         14 . The method of  claim 13 , wherein the EZH2 inhibitor is EPZ-6438 having the following formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         15 . The method of  claim 14 , wherein the EZH2 inhibitor is administered to the subject at a dose of about 100 mg to about 3200 mg daily. 
     
     
         16 . The method of  claim 14 , wherein the EZH2 inhibitor is administered to the subject at a dose of about 100 mg BID to about 1600 mg BID. 
     
     
         17 . The method of  claim 14 , wherein the EZH2 inhibitor is administered to the subject at a dose of about 100 mg BID, 200 mg BID, 400 mg BID, 800 mg BID, or about 1600 mg BID. 
     
     
         18 . The method of  claim 17 , wherein the EZH2 inhibitor is administered to the subject at a dose of 800 mg BID. 
     
     
         19 . The method of  claim 13 , wherein the EZH2 inhibitor is: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         20 . The method of  claim 19 , wherein the EZH2 inhibitor is: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof.