Methods and therapeutic combinations for treating tumors
View Patent ↗Methods and therapeutic combinations useful for increasing cell-mediated anti-tumor responses are described. The methods include administering to a subject a therapeutically effective amount of an Immune Response Modifier Compound and a therapeutically effective amount of one or more immune checkpoint inhibitor compounds.
1. A method of treating a tumor in a subject in need thereof, comprising administering a therapeutically effective amount of a first immune checkpoint inhibitor compound to the subject; and administering a therapeutically effective amount of an IRM compound to the subject; wherein the IRM compound is N-(4-{[4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl]oxy}butyl)octadecanamide, or a pharmaceutically acceptable salt thereof.
2. A therapeutic combination for treating a tumor comprising:
a therapeutically effective amount of a first immune checkpoint inhibitor compound; and a therapeutically effective amount of an IRM compound, wherein the IRM compound is N-(4-{[4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl]oxy}butyl)octadecanamide, or a pharmaceutically acceptable salt thereof.
3. The method of claim 1 , wherein the first immune checkpoint inhibitor compound is incorporated in a first pharmaceutically acceptable formulation.
4. The method or therapeutic combination of claim 3 , wherein the first pharmaceutically acceptable formulation is an aqueous formulation.
5. The method claim 3 , wherein the first pharmaceutically acceptable formulation is injected directly into a tumor.
6. The method of claim 3 , wherein the first pharmaceutically acceptable formulation is administered by intravenous infusion.
7. The method of claim 1 , wherein the IRM compound is incorporated in a second pharmaceutically acceptable formulation.
8. The method of claim 7 , wherein the second pharmaceutically acceptable formulation comprises sesame oil and ethanol.
9. The method of claim 8 , wherein the ethanol is present in the second pharmaceutically acceptable formulation in an amount of from 1 wt-% to 9 wt-%.
10. The method of claim 9 , wherein the ethanol is present in the second pharmaceutically acceptable formulation in an amount from 7 wt-% to 8 wt-%.
11. The method of claim 7 , wherein the IRM compound is incorporated into a liposome formulation.
12. The method of claim 7 , wherein the second pharmaceutically acceptable formulation is injected directly into a tumor.
13. The method of claim 1 , wherein the immune checkpoint inhibitor compound is a CTLA-4 receptor inhibitor, PD-1 receptor inhibitor, PD-L1 inhibitor, PD-L2 inhibitor, a LAG-3 receptor inhibitor, a TIM-3 receptor inhibitor, a BTLA receptor inhibitor, or a KIR receptor inhibitor.
14. The method of claim 1 , wherein the immune checkpoint inhibitor compound is an antibody or antibody fragment.
15. The method of claim 14 , wherein the immune checkpoint inhibitor compound is an anti-CTLA-4 receptor antibody, an anti-PD-1 receptor antibody, an anti-PD-L1 antibody, or an anti-PD-L2, antibody.
16. The method of claim 1 , wherein the tumor is a breast cancer tumor, a bladder cancer tumor, a head and neck cancer tumor, a non-small cell lung cancer tumor, a small cell lung cancer tumor, a colorectal cancer tumor, a gastrointestinal stromal tumor, a gastroesophageal carcinoma, a renal cell cancer tumor, a prostate cancer tumor, a liver cancer tumor, a colon cancer tumor, a pancreatic cancer tumor, an ovarian cancer tumor, a lymphoma, or a cutaneous T-cell lymphoma, or a melanoma.
17. The method of claim 3 further comprising a second immune checkpoint inhibitor compound.
18. The method of claim 17 , wherein the second immune checkpoint inhibitor compound is incorporated in a third pharmaceutically acceptable formulation.
19. The method of claim 18 , wherein the third pharmaceutically acceptable formulation is an aqueous formulation.
20. The method of claim 18 , wherein the third pharmaceutically acceptable formulation is injected directly into a tumor.
21. The method claim 18 , wherein the third pharmaceutically acceptable formulation is administered by intravenous infusion.
22. The method of claim 17 , wherein the first and second immune checkpoint inhibitors are both incorporated in the first pharmaceutically acceptable formulation.
23. A kit for treating a tumor comprising at least one immune checkpoint inhibitor compound; an IRM compound; wherein the IRM compound is N-(4-{[4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl]oxy}butyl)octadecanamide, or a pharmaceutically acceptable salt thereof; and a set of instructions for use.
24. The kit of claim 23 , wherein the at least one immune checkpoint inhibitor compound is a CTLA-4 receptor inhibitor, PD-1 receptor inhibitor, PD-L1 ligand inhibitor, or PD-L2 ligand inhibitor, a LAG-3 receptor inhibitor, a TIM-3 receptor inhibitor, a BTLA receptor inhibitor, a KIR receptor inhibitor, or a combination of any of the foregoing immune checkpoint inhibitor compounds.
25. The kit of claim 23 , wherein the immune checkpoint inhibitor compound is an antibody or an antibody fragment.
26. The kit of claim 24 , wherein the at least one immune checkpoint inhibitor compound is an anti-CTLA-4 receptor antibody, an anti-PD-1 receptor antibody, an anti-PD-L1 antibody, an anti-PD-L2 antibody, or a combination of any of the foregoing antibodies.
27. The kit of any of the claims 23 - 26 , wherein the at least one immune checkpoint inhibitor compound is in the form of a lyophilized solid.
28. The kit of any of the claims 23 - 26 further comprising an aqueous reconstitution solvent.
29. The kit of any of the claims 23 - 26 , wherein the at least one immune checkpoint inhibitor compound is incorporated in a first pharmaceutically acceptable formulation and the N-(4-{[4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl]oxy}butyl)octadecanamide is incorporated in a second pharmaceutically acceptable formulation.
30. The kit of claim 29 , wherein the N-(4-{[4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl]oxy}butyl)octadecanamide is incorporated in a formulation comprising sesame oil and ethanol.