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 a riluzole prodrug having formula:
and an inhibitor of a checkpoint receptor selected from PD-1 and PD-L1, wherein the cancer is bladder cancer, breast cancer, colorectal cancer, gastrointestinal cancer, glioblastoma, lymphoma, melanoma, non-small cell lung cancer, ovarian cancer, prostate cancer, renal cell carcinoma, solid malignancy, and squamous cell carcinoma of head and neck.
2. The method of claim 1 , wherein riluzole prodrug and the checkpoint inhibitor are administered either concurrently or sequentially in time.
3. The method of claim 1 , wherein said checkpoint inhibitor is selected from the group consisting of nivolumab, pembrolizumab, pidilizumab, PDR001, MEDI0680, atezolizumab, durvalumab and combinations thereof.
4. 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.
5. 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 ).
6. The method of claim 3 , 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 ).
7. The method of claim 1 , wherein the cancer is bladder cancer.
8. The method of claim 1 , wherein the cancer is breast cancer.
9. The method of claim 1 , wherein the cancer is colorectal cancer.
10. The method of claim 1 , wherein the cancer is gastrointestinal cancer.
11. The method of claim 1 , wherein the cancer is glioblastoma.
12. The method of claim 1 , wherein the cancer is lymphoma.
13. The method of claim 1 , wherein the cancer is melanoma.
14. The method of claim 1 , wherein the cancer is non-small cell lung cancer.
15. The method of claim 1 , wherein the cancer is ovarian cancer.
16. The method of claim 1 , wherein the cancer is prostate cancer.
17. The method of claim 1 , wherein the cancer is renal cell carcinoma.
18. The method of claim 1 , wherein the cancer is solid malignancy.
19. The method of claim 1 , wherein the cancer is squamous cell carcinoma of head and neck.