Treatment of cancer

Abstract

Provided herein are compositions and methods for the treatment of a hematological malignancy. Also disclosed herein are compositions and methods for the treatment of Ewing's Sarcoma. Said compositions comprise isoform selective pyrrolo-pyrazole PKC inhibitors.

1 .- 35 . (canceled) 
     
     
         36 . A method of treating a hematological malignancy in an individual in need thereof, comprising administering to the individual: (a) a composition comprising 5-{[(2S,5R)-2,5-Dimethyl-4-(tetrahydro-2H-pyran-4-ylmethyl)piperazin-1-yl]carbonyl}-N-(5-fluoro-2-methylpyrimidin-4-yl)-6,6- dimethyl-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-3-amine, or a pharmaceutically acceptable salt thereof; and (b) at least one oncology therapeutic selected from the group consisting of a SYK inhibitor, a dual SYK-JAK inhibitor, a PI3K inhibitor, a JAK-STAT inhibitor, a BCL2 inhibitor, an immunomodulatory agent, an antibody-drug conjugate, an immune checkpoint inhibitor, a PD-1 inhibitor, a TIM-3 inhibitor, a CTLA-4 inhibitor, a bromodomain inhibitor, an EZH2 inhibitor, an HDAC inhibitor, and an IDH2 inhibitor. 
     
     
         37 . (canceled) 
     
     
         38 . The method of  claim 37 , wherein the lymphoma or leukemia is a classical Hodgkin lymphoma, diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, small lymphocytic lymphoma (SLL), chronic lymphocytic leukemia (CLL), mantle cell lymphoma, marginal zone B-cell lymphoma, Burkitt's lymphoma, lymphoplasmacytic lymphoma (Waldenstrom macroglobulinemia), hairy cell leukemia, primary central nervous system (CNS) lymphoma, acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic myeloid leukemia (CIVIL), or chronic myelomonocytic leukemia (CMML). 
     
     
         39 . The method of  claim 36 , wherein the hematological malignancy is a relapsed or refractory hematological malignancy. 
     
     
         40 . (canceled) 
     
     
         41 . The method of  claim 38 , wherein the hematological malignancy is small lymphocytic lymphoma (SLL). 
     
     
         42 . The method of  claim 38 , wherein the hematological malignancy is chronic lymphocytic leukemia (CLL). 
     
     
         43 . The method of  claim 38 , wherein the hematological malignancy is marginal zone B-cell lymphoma. 
     
     
         44 . The method of  claim 38 , wherein the hematological malignancy is diffuse large B-cell lymphoma (DLBCL). 
     
     
         45 . The method of  claim 38 , wherein the hematological malignancy is lymphoplasmacytic lymphoma (Waldenstrom macroglobulinemia). 
     
     
         46 . The method of  claim 41 , wherein the at least one oncology therapeutic is a BCL2 inhibitor. 
     
     
         47 . The method of  claim 42 , wherein the at least one oncology therapeutic is a BCL2 inhibitor. 
     
     
         48 . The method of  claim 41 , wherein the small lymphocytic lymphoma (SLL) is a relapsed or refractory. 
     
     
         49 . The method of  claim 42 , wherein the chronic lymphocytic leukemia (CLL) is a relapsed or refractory. 
     
     
         50 . The method of  claim 48 , wherein the at least one oncology therapeutic is a BCL2 inhibitor. 
     
     
         51 . The method of  claim 49 , wherein the at least one oncology therapeutic is a BCL2 inhibitor.