Therapeutic compositions, combinations, and methods of use

Abstract

This invention relates to methods comprising administering a FAK inhibitor (e.g., VS-6063) in combination with a dual RAF/MEK inhibitor (e.g., CHS 126766) that are useful in the treatment of abnormal cell growth, such as cancer, in a subject such as humans.

1 .- 26 . (canceled) 
     
     
         27 . A method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of C1-15126766, or a pharmaceutically acceptable salt thereof, in combination with VS-6063, or a pharmaceutically acceptable salt thereof. 
     
     
         28 . The method of  claim 27 , wherein the cancer is selected from the group consisting of ovarian cancer, lung cancer, colon cancer, and pancreatic cancer. 
     
     
         29 . (canceled) 
     
     
         30 . The method of  claim 28 , wherein the ovarian cancer is low grade serous ovarian cancer or mucinous ovarian cancer. 
     
     
         31 .- 33 . (canceled) 
     
     
         34 . The method of  claim 27 , wherein the CH5126766 or a pharmaceutically acceptable salt thereof is dosed twice a week. 
     
     
         35 . The method of  claim 27 , wherein the VS-6063 or a pharmaceutically acceptable salt thereof is dosed twice daily. 
     
     
         36 . The method of  claim 27 , wherein the VS-6063 or a pharmaceutically acceptable salt thereof is dosed once daily. 
     
     
         37 . The method of  claim 27 , wherein the CH5126766 or a pharmaceutically acceptable salt thereof and the VS-6063 or a pharmaceutically acceptable salt thereof are dosed for at least three weeks. 
     
     
         38 . (canceled) 
     
     
         39 . The method of  claim 27 , wherein the CH5126766 or a pharmaceutically acceptable salt thereof and the VS-6063 or a pharmaceutically acceptable salt thereof are administered as a cycle comprising administering the CH5126766 or a pharmaceutically acceptable salt thereof and VS-6063 or a pharmaceutically acceptable salt thereof for three weeks and then not administering the CH5126766 or a pharmaceutically acceptable salt thereof and VS-6063 or a pharmaceutically acceptable salt thereof for one week. 
     
     
         40 . The method of  claim 27 , wherein the C1-15126766 or a pharmaceutically acceptable salt thereof is dosed at about 0.5 mg to about 10 mg per administration. 
     
     
         41 . The method of  claim 27 , wherein the CH5126766 or a pharmaceutically acceptable salt thereof is dosed at about 4 mg per administration. 
     
     
         42 . The method of  claim 27 , wherein the C1-15126766 or a pharmaceutically acceptable salt thereof is dosed at 3.2 mg per administration. 
     
     
         43 . (canceled) 
     
     
         44 . The method of  claim 27 , wherein the VS-6063 or a pharmaceutically acceptable salt thereof is dosed at about 100 mg to about 500 rig per administration. 
     
     
         45 - 53 . (canceled) 
     
     
         54 . The method of  claim 27 , wherein the VS-6063 or a pharmaceutically acceptable salt thereof is dosed at about 200 mg per administration. 
     
     
         55 . The method of  claim 27 , wherein the VS-6063 or a pharmaceutically acceptable salt thereof is dosed at about 400 mg per administration. 
     
     
         56 . The method of  claim 27 , wherein the cancer is characterized as having a mutation in EGFR, FGFR, ALK, ROS1, PI3K, NF-1, BRAF, HRAS, KRAS, or NRAS. 
     
     
         57 . The method of  claim 27 , wherein the cancer is characterized as having a mutation in RAS, BRAF, or NF-1. 
     
     
         58 . The method of  claim 27 , wherein the CH5126766 or a pharmaceutically acceptable salt thereof and the VS-6063 or a pharmaceutically acceptable salt thereof are each administered for at least four weeks. 
     
     
         59 . The method of  claim 27 , wherein the pharmaceutically acceptable salt thereof of CH5126766 is a potassium salt of CH5126766. 
     
     
         60 . The method of any  claim 27 , wherein the pharmaceutically acceptable salt thereof of VS-6063 is a hydrochloride salt of VS-6063. 
     
     
         61 . The method of  claim 27 , wherein the cancer is selected from the group consisting of lung cancer, colorectal cancer, pancreatic cancer, ovarian cancer, uterine cancer, and melanoma.