COMBINATION of ATR KINASE INHIBITORS and PD-1/PD-L1 INHIBITORS

Abstract

The present invention covers combinations of at least two components, component A and component B, comprising component A being an inhibitor of ATR kinase, particularly an inhibitor of ATR kinase selected from VX-803, VX-970, AZD-6738, a compound of general formula (I) described herein, a compound of general formula (Ib) described herein and Compound A described infra, and component B being a PD-1/PD-L1 inhibitor described herein. Another aspect of the present invention covers the use of such combinations as described herein for the preparation of a medicament for the treatment or prophylaxis of a disease, particurlarly for the treatment of a hyper-proliferative disease.

1 .- 15 . (canceled) 
     
     
         16 . A combination of at least two components, component A and component B, comprising a component A being an inhibitor of ATR kinase and component B being a PD-1 inhibitor or a PD-L1 inhibitor, in which said component A has the formula: 
       
         
           
           
               
               
           
         
         or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a pharmaceutically acceptable salt 
         thereof, and in which said component B is pembrolizumab as PD-1 inhibitor, or atezolizumab as PDL1 
         inhibitor, said combination being for use in the treatment of a hyperproliferative disease, said hyperproliferative disease being lymphoma, lung carcinoma or colon carcinoma, 
         wherein said component B is to be administered prior to the first administration of component A. 
       
     
     
         17 . The combination of  claim 16 , wherein component B is pembrolizumab. 
     
     
         18 . The combination of  claim 16 , wherein component B is atezolizumab. 
     
     
         19 . A kit, comprising:
 Component A, as defined in  claim 16 ;   Component B, as defined in  claim 16 ; and, optionally,   Component C, wherein component C is one or more further pharmaceutical agents.   
     
     
         20 . The kit of  claim 19 , wherein component B is pembrolizumab. 
     
     
         21 . The kit of  claim 19 , wherein component B is atezolizumab. 
     
     
         22 . A pharmaceutical composition comprising a combination as defined in  claim 16  together with one or more pharmaceutically acceptable excipients. 
     
     
         23 . The pharmaceutical composition of  claim 22 , wherein component A and component B are present in a joint formulation. 
     
     
         24 . The pharmaceutical composition of  claim 22 , wherein component A and component B are present in separate formulations. 
     
     
         25 . The pharmaceutical composition of  claim 22 , wherein component B is pembrolizumab. 
     
     
         26 . The pharmaceutical composition of  claim 22 , wherein component B is atezolizumab.