Combination of anti-ctla4 antibody with dasatinib for the treatment of proliferative diseases

Abstract

Compositions and methods are disclosed which are useful of the treatment and prevention of proliferative disorders.

1 - 14 . (canceled) 
     
     
         15 . A method for the treatment of cancer, comprising the administration to a mammal in need thereof a synergistic, therapeutically effective amount of an anti-CTLA-4 antibody with a chemotherapeutic agent, wherein said chemotherapeutic agent is a DNA double strand break inducing agent. 
     
     
         16 . The method according to  claim 15 , wherein said chemotherapeutic agent is a topoisomerase II inhibitor. 
     
     
         17 . The method according to  claim 16 , wherein said chemotherapeutic agent is 4′-Demethylepipodophyllotoxin 9-[4,6-O—(R)-ethylidene-β-D-glucopyranoside], 4′-(dihydrogen phosphate), or a pharmaceutically acceptable salt, solvate, or hydrate thereof. 
     
     
         18 . The method according to  claim 15 , wherein said anti-CTLA-4 antibody is selected from the group consisting of: ipilimumab and tremelimumab. 
     
     
         19 . The method according to  claim 15 , wherein said anti-CTLA-4 antibody is ipilimumab. 
     
     
         20 . The method according to  claim 15 , wherein said anti-CTLA-4 antibody is tremelimumab. 
     
     
         21 . The method according to  claim 15 , wherein said cancer is a solid tumor. 
     
     
         22 . The method according to  claim 21 , wherein said solid tumor is selected from the group consisting of: lung cancer, sarcoma, fibrosarcoma, pancreatic cancer, prostate cancer, and colon cancer. 
     
     
         23 . The method according to  claim 15 , wherein said method is for the treatment of a tumor refractory to said chemotherapeutic agent. 
     
     
         24 . The method according to  claim 15 , wherein said chemotherapeutic agent is administered before the administration of said anti-CTLA4 antibody. 
     
     
         25 . The method according to  claim 15 , wherein said chemotherapeutic agent is administered essentially simultaneously with the administration of said anti-CTLA4 antibody. 
     
     
         26 . The method according to  claim 15 , wherein said cancer treatment further comprises an anti-proliferative cytotoxic agent either alone or in combination with radiation therapy. 
     
     
         27 . The method according to  claim 17 , wherein said chemotherapeutic agent is administered at a dose of about 50 mg. 
     
     
         28 . The method according to  claim 17 , wherein said chemotherapeutic agent is administered at a dose equivalent to 100 mg etoposide. 
     
     
         29 . The method according to  claim 15 , wherein said chemotherapeutic agent is administered daily. 
     
     
         30 . The method according to  claim 15 , wherein said anti-CTLA4 antibody is administered about every three weeks.