Pharmaceutical combination of mek inhibitor and b-raf inhibitors

Abstract

A novel combination comprising the MEK inhibitor N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)6,8-dimethyl;-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide, or solvate thereof, with a B-Raf inhibitor, particularly N-{3-[5-(2-Amino-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising the same and methods of using such combinations and compositions in the treatment of conditions in which the inhibition of MEK and/or B-Raf is beneficial, eg. melanoma.

We claim: 
     
         1 . A combination comprising:
 (i) a compound of formula (I)   
       
         
           
           
               
               
           
         
         or solvate thereof; and 
         (ii) a compound of formula (II) 
       
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . A combination according to  claim 1  wherein compound (i) is in the form of the dimethylsulfoxide solvate and the compound (ii) is in the form of the methanesulfonate salt. 
     
     
         3 . A combination kit comprising a combination according  claim 1  together with a pharmaceutically acceptable carrier or carriers. 
     
     
         4 . A pharmaceutical composition comprising a combination according to  claim 1  together with a pharmaceutically acceptable diluent or carrier. 
     
     
         5 . A method of treating melanoma in a human in need thereof which comprises the administration of a therapeutically effective amount of
 (i) a compound of formula (I)   
       
         
           
           
               
               
           
         
         or solvate thereof; and 
         (ii) a compound of formula (II) 
       
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         6 . The method of  claim 5 , wherein compound (i) is in the form of the dimethylsulfoxide solvate. 
     
     
         7 . The method of  claim 5 , wherein the compound (ii) is in the form of the methanesulfonate salt. 
     
     
         8 . The method of  claim 5 , wherein the melanoma is metastatic melanoma. 
     
     
         9 . The method of  claim 5 , wherein the melanoma is BRAFV600E mutant melanoma.