Methods and compositions for treating abnormal cell growth

Abstract

The present invention relates to, inter alia, combinations, methods, compositions, and oral dosage forms of a FAK inhibitor and a MEK inhibitor, for treating abnormal cell growth (e.g., cancer).

1 . A method of treating a subject having cancer, the method comprising administering to the subject a therapeutically effective amount of a FAK inhibitor in combination with a MEK inhibitor, thereby treating the subject. 
     
     
         2 . The method of  claim 1 , wherein the FAK inhibitor or the MEK inhibitor is administered orally. 
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein the FAK inhibitor is VS-6063, or a pharmaceutically acceptable salt thereof. 
     
     
         5 . The method of  claim 4 , wherein VS-6063, or a pharmaceutically acceptable salt thereof is administered at from 10 to 2000 mg, 50 to 1500 mg, 100 to 1000 mg, 500 to 1000 mg, or 700 to 900 mg, per day. 
     
     
         6 . The method of  claim 4 , wherein VS-6063, or a pharmaceutically acceptable salt thereof is administered at from 10 to 1000 mg, 50 to 750 mg, 100 to 750 mg, 250 to 500 mg, or 300 to 500 mg, twice daily. 
     
     
         7 - 10 . (canceled) 
     
     
         11 . The method of  claim 4 , wherein VS-6063, or a pharmaceutically acceptable salt thereof is administered as a composition. 
     
     
         12 . The method of  claim 1 , wherein VS-6063, or a pharmaceutically acceptable salt thereof is present in the composition comprising 5 to 30%, 10 to 30%, 10 to 20%, 12 to 15%, or 13% weight of VS-6063, or a pharmaceutically acceptable salt thereof, per weight of the composition. 
     
     
         13 . The method of  claim 1 , wherein the MEK inhibitor is trametinib, or a pharmaceutically acceptable salt thereof. 
     
     
         14 . The method of  claim 1 , wherein the MEK inhibitor is GDC-0623, or a pharmaceutically acceptable salt thereof. 
     
     
         15 . The method of  claim 1 , wherein the MEK inhibitor is cobimetinib, or a pharmaceutically acceptable salt thereof. 
     
     
         16 . The method of  claim 1 , wherein the MEK inhibitor is AZD6244, or a pharmaceutically acceptable salt thereof. 
     
     
         17 . The method of  claim 1 , wherein the MEK inhibitor is pimasertib, or a pharmaceutically acceptable salt thereof. 
     
     
         18 - 24 . (canceled) 
     
     
         25 . The method of  claim 1 , wherein the cancer is a mesothelioma, neurofibromatosis, neurofibromatosis type 2, neurofibromatosis type 1, renal cancer lung cancer, non small cell lung cancer, liver cancer, thyroid cancer, ovarian cancer, breast cancer, a nervous system tumor, schwannoma, meningioma, schwannomatosis, neuroma acoustic, adenoid cystic carcinoma, ependymoma, ependymal tumors, or any other tumor which exhibits decreased merlin expression and/or mutation, and/or deletion and/or promotor hypermethylation of the NF-2 gene. 
     
     
         26 - 27 . (canceled) 
     
     
         28 . The method of  claim 1 , wherein the FAK inhibitor and the MEK inhibitor are administered at amounts that result in a synergistic effect. 
     
     
         29 . The method of  claim 1 , wherein the administration is performed in combination with administration of an additional agent. 
     
     
         30 . The method of  claim 29 , wherein the additional agent is a cancer therapy. 
     
     
         31 . The method of  claim 30 , wherein the cancer therapy is chemotherapy, targeted therapies, immunotherapy, or hormonal therapy. 
     
     
         32 . The method of  claim 30 , wherein the cancer therapy comprises administration of an anti-inflammatory agent, analgesic agent, or antiemetic agent. 
     
     
         33 . A composition or dosage form comprising a FAK inhibitor and a MEK inhibitor, wherein the inhibitors are present in each case in free form or in the form of a pharmaceutically acceptable salt or hydrate thereof, and optionally at least one pharmaceutically acceptable carrier, for simultaneous, separate, or sequential use. 
     
     
         34 . A composition or dosage form comprising a FAK inhibitor and a MEK inhibitor, wherein the inhibitors are present in each case in free form or in the form of a pharmaceutically acceptable salt or hydrate thereof, and wherein the inhibitors are present in a synergistic ratio. 
     
     
         35 - 39 . (canceled)