Combination therapy for treating cancer

Abstract

The disclosure relates to methods, compounds for use and medicaments for the treatment of cancer comprising administering to a subject in need thereof a first agent in a therapeutically effective amount and one or more second agents each in a therapeutically effective amount. In some embodiments, the first agent comprises an EZH2 inhibitor. In certain embodiments, the first agent is tazemetostat or a pharmaceutically acceptable salt thereof and the methods of the disclosure are used to treat lung cancer, e.g., non-small cell lung cancer.

1 . A method for treatment of non-small cell lung cancer (NSCLC) comprising administering to a subject in need thereof
 (a) a first agent in a therapeutically effective amount, wherein the first agent comprises an EZH2 inhibitor, and   (b) one or more second agents in a therapeutically effective amount.   
     
     
         2 . The method of  claim 1 , wherein the EZH2 inhibitor is tazemetostat or a pharmaceutically acceptable salt thereof. 
     
     
         3 . A method of inhibiting or decreasing growth, viability, survival, or proliferation of a cancer cell comprising contacting the cell with
 (a) an effective amount of EZH2 inhibitor, and   (b) one or more second agents.   
     
     
         4 . The method of  claim 1 , wherein the one or more second agents comprise a standard of care agent. 
     
     
         5 . The method of  claim 1 , wherein the one or more second agents comprise an alkylating agent or an alkylating-like agent, an antineoplastic agent, a mitotic inhibitor, a tubulin polymerization inhibitor, an antimetabolite, a DNA methyltransferase (DNMT) inhibitor, a histone deacetylase (HDAC) inhibitor, a topoisomerase inhibitor, an epidermal growth factor receptor (EGFR) inhibitor, an inhibitor of EGFR and ErbB2, an inhibitor of EGFR and human epidermal growth factor receptor 2 (Her2), cyclin dependent kinase (CDK) 4/6 inhibitor, a mitogen-activated protein kinase (MEK) inhibitor, a BRAF inhibitor, a phosphoinositide 3-kinase (PI3K) inhibitor, a Wee1 inhibitor, a poly (ADP-ribose) polymerase (PARP) inhibitor, a glucocorticoid receptor agonist, a retinoic acid receptor agonist, a CBP/p300 inhibitor, or a combination thereof. 
     
     
         6 . The method of  claim 5 , wherein the one or more second agents comprise an alkylating agent or an alkylating-like agent, an antineoplastic agent, or a combination thereof. 
     
     
         7 . The method of  claim 5 , wherein the one or more second agents comprise a mitotic inhibitor, a tubulin polymerization inhibitor, or a combination thereof. 
     
     
         8 . The method of  claim 5 , wherein the one or more second agents comprise an antimetabolite. 
     
     
         9 . The method of  claim 5 , wherein the one or more second agents comprise a DNA methyltransferase (DNMT) inhibitor, a histone deacetylase (HDAC) inhibitor, or a combination thereof. 
     
     
         10 . The method of  claim 5 , wherein the one or more second agents comprise a topoisomerase inhibitor. 
     
     
         11 . The method of  claim 5 , wherein the one or more second agents comprise an epidermal growth factor receptor (EGFR) inhibitor, an inhibitor of EGFR and ErbB2, an inhibitor of EGFR and human epidermal growth factor receptor 2 (Her2), or a combination thereof. 
     
     
         12 . The method of  claim 5 , wherein the one or more second agents comprise a cyclin dependent kinase (CDK) 4/6 inhibitor. 
     
     
         13 . The method of  claim 5 , wherein the one or more second agents comprise a mitogen-activated protein kinase (MEK) inhibitor. 
     
     
         14 . The method of  claim 5 , wherein the one or more second agents comprise a BRAF inhibitor. 
     
     
         15 . The method of  claim 5 , wherein the one or more second agents comprise a phosphoinositide 3-kinase (PI3K) inhibitor. 
     
     
         16 . The method of  claim 5 , wherein the one or more second agents comprise a Wee1 inhibitor. 
     
     
         17 . The method of  claim 5 , wherein the one or more second agents comprise a poly (ADP-ribose) polymerase (PARP) inhibitor. 
     
     
         18 . The method of  claim 5 , wherein the one or more second agents comprise a glucocorticoid receptor agonist, a retinoic acid receptor agonist, or a combination thereof. 
     
     
         19 . The method of  claim 5 , wherein the one or more second agents comprise a CBP/p300 inhibitor. 
     
     
         20 . The method of  claim 1 , wherein the amount of the EZH2 inhibitor is between about 100 mg and about 1600 mg.