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 . (canceled) 
     
     
         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 - 12 . (canceled) 
     
     
         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 - 21 . (canceled) 
     
     
         22 . The method of  claim 1 , wherein the cancer is a solid tumor, soft tissue tumor, metastasis, or non-solid cancer. 
     
     
         23 . The method of  claim 1 , wherein the cancer is solid tumor. 
     
     
         24 . The method of  claim 23 , wherein the solid tumor is a malignancy of an organ selected from the group consisting of lung, breast, lymphoid, gastrointestinal, and genitourinary tracts, pharynx, prostate, and ovary. 
     
     
         25 . The method of  claim 1 , wherein the cancer is a mesothelioma; neurofibromatosis; renal cancer; lung cancer, non small cell lung cancer; liver cancer; thyroid cancer; ovarian; 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 . The method of  claim 1 , wherein the cancer is selected from the group comprising mesothelioma, breast cancer, ovarian cancer, lung cancer, and non-hematolotic malignancies. 
     
     
         27 . The method of  claim 1 , wherein the cancer is selected from the group comprising melanoma, colorectal cancer, leukemia, adenocarcinoma, solid tumor. 
     
     
         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 - 33 . (canceled) 
     
     
         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 . A composition or dosage form comprising a therapeutically effective amount of a FAK inhibitor and a MEK inhibitor. 
     
     
         36 . The composition or dosage form of  claim 34 , wherein the FAK inhibitor is VS-6063, or a pharmaceutically acceptable salt thereof. 
     
     
         37 . The composition or dosage form of  claim 36 , wherein VS-6063, or a pharmaceutically acceptable salt thereof is administered at 400 or less mg/twice daily. 
     
     
         38 - 39 . (canceled)