Use of riluzole, riluzole prodrugs or riluzole analogs with immunotherapies to treat cancers

Abstract

Disclosed are methods of treating cancer using a combination of an immunotherapeutic agent, such as, for example, a PD-1, PD-L1 or CTLA-4 checkpoint inhibitor, and a glutamate modulating agent such as riluzole or trigriluzole. Pharmaceutical compositions including the immunotherapeutic agents and glutamate modulating agents are also disclosed.

What is claimed is: 
     
         1 . A method of treating cancer by administering a combination therapy to a patient in need thereof comprising of an effective amount of riluzole and a checkpoint inhibitor. 
     
     
         2 . The method of  claim 1  wherein riluzole and the checkpoint inhibitor are administered either concurrently or sequentially in time. 
     
     
         3 . The method of  claim 1  wherein said checkpoint inhibitor targets PD-1, PD-L1 or CTLA-4. 
     
     
         4 . The method of  claim 1  wherein said checkpoint inhibitor is selected from the group consisting of nivolumab, pembrolizumab, pidilizumab, ipilimumab, PDR001, MEDI0680, atezolizumab, durvalumab and combinations thereof. 
     
     
         5 . The method of  claim 1  wherein said riluzole is in the form of an analog or prodrug of riluzole, or pharmaceutically acceptable salts, solvates, anomers, enantiomers, or hydrates thereof. 
     
     
         6 . The method of  claim 1  wherein said combination of riluzole and checkpoint inhibitor is administered in combination or sequentially with other anti-cancer standard of care treatments. 
     
     
         7 . The method of  claim 1  wherein said combination is riluzole and an anti-PD1 or anti-PD-L1 and the cancer treated is glioblastoma. 
     
     
         8 . The method of  claim 1  wherein said combination is riluzole and an anti-PD1 or anti-PD-L1 and the cancer treated is melanoma. 
     
     
         9 . The method of  claim 5  wherein the prodrug has the following formula: 
       
         
           
           
               
               
           
         
       
     
     
         10 . The method of  claim 1  wherein the riluzole and the checkpoint inhibitor are capable of providing a Mouse Survival Ratio of at least 2.0 at day 60 (MSR 60 ). 
     
     
         11 . The method of  claim 4  wherein the riluzole and the checkpoint inhibitor are capable of providing a Mouse Survival Ratio of at least 2.0 at day 60 (MSR 60 ). 
     
     
         12 . The method of  claim 5  wherein the prodrug of riluzole and the checkpoint inhibitor are capable of providing a Mouse Survival Ratio of at least 2.0 at day 60 (MSR 60 ). 
     
     
         13 . The method of  claim 9  wherein the prodrug of riluzole and the checkpoint inhibitor are capable of providing a Mouse Survival Ratio of at least 2.0 at day 60 (MSR 60 ).