Combinations of Cabozantinib and Atezolizumab to Treat Cancer

Abstract

This invention relates to the combination of cabozantinib and atezolizumab to treat locally advanced or metastatic solid tumors, particularly advanced urothelial cancer or renal cell carcinoma.

1 . A method of treating locally advanced or metastatic solid tumors, comprising administering a patient in need of such treatment a compound of formula I: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof or a pharmaceutical composition comprising the compound of formula I or the pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, wherein: 
         R 1  is halo; 
         R 2  is halo; and 
         Q is CH or N; 
         in combination with atezolizumab. 
       
     
     
         2 . The method of  claim 1 , wherein the compound of formula I is compound 1, or a pharmaceutically acceptable salt thereof. 
       
         
           
           
               
               
           
         
       
     
     
         3 . The method of  claim 2 , wherein compound 1 is administered as the L-malate salt (or S-malate salt). 
     
     
         4 . The method of  claim 2 , wherein compound 1 is administered as the D-malate salt (or R-malate salt). 
     
     
         5 . The method of any one of  claims 2 - 4  wherein atezolizumab is administered intravenously (IV). 
     
     
         6 . The method of any one of  claims 1 - 5 , wherein the locally advanced or metastatic solid tumors is advanced urothelial carcinoma (UC), renal cell carcinoma (RCC), castration-recurrent prostate cancer (CRPC) or non-small cell lung cancer (NSCLC). 
     
     
         7 . The method of any one of  claims 2 - 6 , wherein Compound 1 or a pharmaceutically acceptable salt thereof and atezolizumab are administered concurrently or sequentially. 
     
     
         8 . The method of  claim 6 , wherein up to and including 1,200 mg of atezolizumab is administered to the patient once every three weeks in combination with 100 mg, 95 mg, 90 mg, 85 mg, 80 mg, 75 mg, 70 mg, 65 mg, 60 mg, 55 mg, 50 mg, 45 mg, 40 mg, 35 mg, 30 mg, 25 mg, 20 mg, 15 mg, 10 mg, or 5 mg of compound 1, or a pharmaceutically acceptable salt thereof, once daily with fasting. 
     
     
         9 . The method of  claim 8 , wherein up to and including 1,200 mg of atezolizumab is administered to the patient once every three weeks in combination with 60 mg, 40 mg, or 20 mg of compound 1, or a pharmaceutically acceptable salt thereof, once daily with fasting. 
     
     
         10 . The method of  claim 6 , wherein up to and including 1,100 mg of atezolizumab is administered to the patient once every three weeks in combination with 100 mg, 95 mg, 90 mg, 85 mg, 80 mg, 75 mg, 70 mg, 65 mg, 60 mg, 55 mg, 50 mg, 45 mg, 40 mg, 35 mg, 30 mg, 25 mg, 20 mg, 15 mg, 10 mg, or 5 mg of compound 1, or a pharmaceutically acceptable salt thereof, once daily with fasting. 
     
     
         11 . The method of  claim 10 , wherein up to and including 1,100 mg of atezolizumab is administered to the patient once every three weeks in combination with 60 mg, 40 mg, or 20 mg of compound 1, or a pharmaceutically acceptable salt thereof, once daily with fasting. 
     
     
         12 . The method of  claim 6 , wherein up to and including 1,000 mg of atezolizumab is administered to the patient once every three weeks in combination with 100 mg, 95 mg, 90 mg, 85 mg, 80 mg, 75 mg, 70 mg, 65 mg, 60 mg, 55 mg, 50 mg, 45 mg, 40 mg, 35 mg, 30 mg, 25 mg, 20 mg, 15 mg, 10 mg, or 5 mg of compound 1, or a pharmaceutically acceptable salt thereof, once daily with fasting. 
     
     
         13 . The method of  claim 12 , wherein up to and including 1,000 mg of atezolizumab is administered to the patient once every three weeks in combination with 60 mg, 40 mg, or 20 mg of compound 1, or a pharmaceutically acceptable salt thereof, once daily with fasting. 
     
     
         14 . The method of  claim 6 , wherein up to and including 900 mg of atezolizumab is administered to the patient once every three weeks in combination with 100 mg, 95 mg, 90 mg, 85 mg, 80 mg, 75 mg, 70 mg, 65 mg, 60 mg, 55 mg, 50 mg, 45 mg, 40 mg, 35 mg, 30 mg, 25 mg, 20 mg, 15 mg, 10 mg, or 5 mg of compound 1, or a pharmaceutically acceptable salt thereof, once daily with fasting. 
     
     
         15 . The method of  claim 14 , wherein up to and including 900 mg of atezolizumab is administered to the patient once every three weeks in combination with 60 mg, 40 mg, or 20 mg of compound 1, or a pharmaceutically acceptable salt thereof, once daily with fasting. 
     
     
         16 . The method of any one of  claims 8 - 15 , wherein Compound 1, or a pharmaceutically acceptable salt thereof, and atezolizumab are administered concurrently or sequentially. 
     
     
         17 . The method of any one of  claims 7 - 16 , wherein the atezolizumab is administered intravenously via infusion over 60 minutes or 30 minutes. 
     
     
         18 . The method of any one of  claims 1 - 17 , wherein a complete serological response is observed in patients being treated with the combination. 
     
     
         19 . The method of any one of  claims 1 - 17 , wherein a serological partial response is observed in patients being treated with the combination. 
     
     
         20 . The method of any one of  claims 1 - 17 , wherein stable disease is observed in patients being treated with the combination.