USE OF RILUZOLE, RILUZOLE PRODRUGS OR RILUZOLE ANALOGS WITH IMMUNOTHERAPIES TO TREAT CANCERS
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.
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 ).