Combination therapy for treating cancer

Abstract

The present disclosure relates to compositions comprising inhibitors of human histone methyltransferase EZH2 and one or more other therapeutic agents (such as tyrosine kinase inhibitors or VEGF/VEGFR inhibitors), particularly anticancer agents such as sunitinib, and methods of combination therapy for administering to subjects in need thereof for the treatment of cancer.

1 . A method for treating cancer in a patient in need thereof comprising administering a therapeutically effective amount of an EZH2 inhibitor and one or more tyrosine kinase inhibitors. 
     
     
         2 . The method of  claim 1 , wherein the cancer is resistant to tyrosine kinase inhibitor treatment. 
     
     
         3 . The method of  claim 1 , wherein the one or more tyrosine kinase inhibitors are VEGF/VEGFR inhibitors. 
     
     
         4 . A method for treating cancer in a patient in need thereof comprising administering a therapeutically effective amount of an EZH2 inhibitor and one or more VEGF/VEGFR inhibitors. 
     
     
         5 . The method of  claim 1 , wherein the cancer is resistant to VEGF/VEGFR inhibitor treatment. 
     
     
         6 . The method of  claim 1 , wherein the EZH2 inhibitor is Compound 44 having the following formula: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof. 
     
     
         7 . The method of  claim 1 , wherein the EZH2 inhibitor is: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof. 
     
     
         8 . The method of  claim 1 , wherein the EZH2 inhibitor is GSK-126. 
     
     
         9 . The method of  claim 1 , wherein the one or more tyrosine kinase inhibitors are selected from erlotinib (Tarceva); gefitinib (Iressa); imatinib (Gleevec); sorafenib (Nexavar); sunitinib (Sutent); trastuzumab (Herceptin); bevacizumab (Avastin); rituximab (Rituxan); lapatinib (Tykerb); cetuximab (Erbitux); panitumumab (Vectibix); everolimus (Afinitor); alemtuzumab (Campath); gemtuzumab (Mylotarg); temsirolimus (Torisel); pazopanib (Votrient); dasatinib (Sprycel); nilotinib (Tasigna); vatalanib (Ptk787; ZK222584); CEP-701; SU5614; MLN518; XL999; VX-322; Azd0530; BMS-354825; SKI-606 CP-690; AG-490; WHI-P154; WHI-P131; AC-220; and AMG888. 
     
     
         10 . The method of  claim 1 , wherein the one or more tyrosine kinase inhibitors includes sunitinib. 
     
     
         11 . The method of  claim 1 , wherein the one or more VEGF/VEGFR inhibitors are selected from bevacizumab (Avastin); sorafenib (Nexavar); sunitinib (Sutent); ranibizumab; pegaptanib; vandetinib; E7080; Zd6474; PKC-412; Vatalanib (Ptk787 or ZK222584); and motesanib diphosphate. 
     
     
         12 . The method of  claim 4 , wherein the one or more VEGF/VEGFR inhibitors includes sunitinib. 
     
     
         13 . The method of  claim 1 , wherein the EZH2 inhibitor and the one or more tyrosine kinase inhibitors are administered simultaneously or sequentially. 
     
     
         14 . The method of  claim 1 , wherein the EZH2 inhibitor is administered prior to administration of the one or more tyrosine kinase inhibitors. 
     
     
         15 . The method of  claim 4 , wherein the EZH2 inhibitor and the one or more VEGF/VEGFR inhibitors are administered simultaneously or sequentially. 
     
     
         16 . The method of  claim 4 , wherein the EZH2 inhibitor is administered prior to administration of the one or more VEGF/VEGFR inhibitors. 
     
     
         17 . The method of  claim 1 , wherein the cancer is renal cell carcinoma.