Combination therapies for inhibition of ttk protein kinase

Abstract

Provided herein are methods of treating cancer using an effective amount of a compound represented by the formula: (I) or a pharmaceutically acceptable salt thereof and an effective amount of an immune checkpoint inhibitor. Also provided are compositions comprising the same compound represented by the formula shown above or a pharmaceutically acceptable salt thereof and an immune checkpoint inhibitor.

1 . A method for treating colon cancer, comprising:
 administering to a subject an effective amount of a compound represented by the formula:   
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof and an effective amount of a PD-L1 inhibitor. 
       
     
     
         2 . The method according to  claim 1 , wherein the PD-L1 inhibitor is an antibody or an antigen binding fragment thereof. 
     
     
         3 . The method according to  claim 1 , wherein the PD-L1 inhibitor is a monoclonal antibody or an antigen binding fragment thereof. 
     
     
         4 - 7 . (canceled) 
     
     
         8 . The method according to  claim 1 , wherein the PD-L1 inhibitor restores anti-tumor T-cell activity. 
     
     
         9 . The method according to  claim 1 , wherein the PD-L1 inhibitor blocks T-cell-inhibitory cell activity. 
     
     
         10 . The method according to  claim 1 , wherein the PD-L1 inhibitor is one selected from atezolizumab, avelumab and durvalumab. 
     
     
         11 - 12 . (canceled) 
     
     
         13 . The method according to  claim 1 , wherein the PD-L1 inhibitor is one selected from JS003, SHR-1316, KN035 and BMS-936559. 
     
     
         14 - 16 . (canceled) 
     
     
         17 . A pharmaceutical composition comprising a compound represented by the formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof and a PD-L1 inhibitor. 
       
     
     
         18 . The pharmaceutical composition according to  claim 17 , wherein the PD-L1 inhibitor is an antibody or an antigen binding fragment thereof. 
     
     
         19 . The pharmaceutical composition according to  claim 17 , wherein the PD-L1 inhibitor is a monoclonal antibody or an antigen binding fragment thereof. 
     
     
         20 - 23 . (canceled) 
     
     
         24 . The pharmaceutical composition according to  claim 17 , wherein the PD-L1 inhibitor restores anti-tumor T cell activity. 
     
     
         25 . The pharmaceutical composition according to  claim 17 , wherein the PD-L1 inhibitor blocks T-cell-inhibitory cell activity. 
     
     
         26 . The pharmaceutical composition according to  claim 17 , wherein the PD-L1 inhibitor is one selected from atezolizumab, avelumab and durvalumab. 
     
     
         27 - 28 . (canceled) 
     
     
         29 . The pharmaceutical composition according to  claim 17 , wherein the L1 inhibitor is one selected from JS003, SHR-1316, KN035 and BMS-936559.