Combination therapy for treating malignancies

Abstract

Provided are methods and compositions for treating cancers in patients carrying an IDH2 mutation using a combination of an inhibitor of a mutant IDH2 enzyme and a DNA demethylating agent.

What is claimed is: 
     
         1 . A pharmaceutical composition comprising 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol, or a pharmaceutically acceptable salt, solvate, tautomer, stereoisomer, isotopologue, prodrug, metabolite, or a polymorph thereof, and azacitidine. 
     
     
         2 . A method of treating a hematological malignancy comprising administering to a subject in need thereof the pharmaceutical composition of  claim 1 , wherein the hematological malignancy is a malignancy characterized by the presence of a mutant allele of IDH2. 
     
     
         3 . The method of  claim 2 , wherein the IDH2 mutation is an IDH2 R140Q or R172K mutation. 
     
     
         4 . The method of  claim 2 , wherein the malignancy is acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), myeloid sarcoma, multiple myeloma, lymphoma (e.g., T-cell lymphoma or B-cell lymphoma), angioimmunoblastic T-cell lymphoma (AITL) or blastic plasmacytoid dendritic cell neoplasm. 
     
     
         5 . The method of any one of  claim 2 , wherein the malignancy is acute myelogenous leukemia. 
     
     
         6 . The method of  claim 5 , wherein the acute myelogenous leukemia newly diagnosed. 
     
     
         7 . A method of treating a solid tumor comprising administering to a subject in need thereof the pharmaceutical composition of  claim 1 , wherein the solid tumor is characterized by the presence of a mutant allele of IDH2.