Formulations and methods for the treatment of cancers

Abstract

The present invention is directed to a formulation for treating cancer comprising an androgen receptor signaling inhibitor and a B-cell-lymphoma-2 inhibitor, which may further comprising a Bromodomain-and-Extra-Terminal protein inhibitor or a phosphoinositide 3-kinase inhibitor.

What is claimed is: 
     
         1 . A formulation, comprising:
 an androgen receptor signaling inhibitor; and   a B-cell lymphoma 2 inhibitor.   
     
     
         2 . The formulation of  claim 1  wherein the androgen receptor signaling inhibitor is enzalutamide. 
     
     
         3 . The formulation of  claim 2 , wherein enzalutamide is contained in said formulation in a concentration of about 5 mg/ml to about 10.0 mg/ml 
     
     
         4 . The formulation of  claim 1 , wherein the B-cell lymphoma 2 inhibitor is venetoclax. 
     
     
         5 . The formulation of  claim 4 , wherein venetoclax is contained in said formulation in a concentration of about 10 mg/ml to about 15 mg/ml. 
     
     
         6 . A pharmaceutical composition comprising the formulation of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         7 . The formulation of  claim 1 , further comprising:
 a Bromodomain and Extra-Terminal protein inhibitor.   
     
     
         8 . The formulation of  claim 7 , wherein the Bromodomain and Extra-Terminal protein inhibitor is JQ1. 
     
     
         9 . The formulation of  claim 8 , wherein JQ1 is contained in said formulation in a concentration of about 10 mg/ml to about 15 mg/ml. 
     
     
         10 . A pharmaceutical composition comprising the formulation of  claim 7  and a pharmaceutically acceptable carrier. 
     
     
         11 . The formulation of  claim 1 , further comprising:
 a phosphoinositide 3-kinase inhibitor.   
     
     
         12 . The formulation of  claim 11 , wherein the phosphoinositide 3-kinase inhibitor is NVP-BEZ235. 
     
     
         13 . A pharmaceutical composition comprising the formulation of  claim 11  and a pharmaceutically acceptable carrier. 
     
     
         14 . A method for inhibiting growth of a tumor in a castration resistant prostate cancer comprising the step of:
 contacting cells in the tumor with a pharmacologically effective amount of the formulation of  claim 1 .   
     
     
         15 . A method for inhibiting growth of a tumor in a castration resistant prostate cancer comprising the step of:
 contacting cells in the tumor with a pharmacologically effective amount of the formulation of  claim 7 .   
     
     
         16 . A method for inhibiting growth of a tumor in a castration resistant prostate cancer comprising the step of:
 contacting cells in the tumor with a pharmacologically effective amount of the formulation of  claim 11 .   
     
     
         17 . A method for treating a prostate cancer in a subject in need of such treatment, comprising the step of:
 administering to said subject a pharmacologically effective amount of an androgen receptor signaling inhibitor and a B-cell lymphoma 2 inhibitor.   
     
     
         18 . The method of  claim 17 , wherein said inhibitors are administered sequentially or simultaneously. 
     
     
         19 . The method of  claim 17 , further comprising:
 administering to said subject a pharmacologically effective amount of a Bromodomain and Extra-Terminal protein inhibitor.   
     
     
         20 . The method of  claim 17 , further comprising:
 administering to said subject a pharmacologically effective amount of a phosphoinositide 3-kinase inhibitor.   
     
     
         21 . The method of  claim 17 , wherein said prostate cancer is an androgen dependent prostate cancer, an androgen independent prostate cancer, an androgen receptor negative prostate cancer, or a castration resistant prostate cancer. 
     
     
         22 . A method for treating a cancer in a subject in need of such treatment, comprising the step of:
 administering either sequentially or simultaneously to said subject a pharmacologically effective amount of an androgen receptor signaling inhibitor, a B-cell lymphoma 2 inhibitor, a Bromodomain and Extra-Terminal protein inhibitor, and a phosphoinositide 3-kinase inhibitor.   
     
     
         23 . The method of  claim 22 , wherein the androgen receptor signaling inhibitor is enzalutamide. 
     
     
         24 . The method of  claim 22 , wherein the B-cell lymphoma 2 inhibitor is venetoclax. 
     
     
         25 . The method of  claim 22 , wherein the Bromodomain and Extra-Terminal protein inhibitor is JQ1. 
     
     
         26 . The method of  claim 22 , wherein the phosphoinositide 3-kinase inhibitor is NVP-BEZ235. 
     
     
         27 . The method of  claim 22 , wherein the cancer is a prostate cancer. 
     
     
         28 . The method of  claim 22 , wherein the prostate cancer is a castration resistant prostate cancer.