Methods and therapeutic combinations for treating tumors

Patent metadata

Field	Value
Publication number	US-9980956-B2
Application number	US-201515500618-A
Country	US
Kind code	B2
Filing date	Jul 31, 2015
Priority date	Aug 1, 2014
Publication date	May 29, 2018
Grant date	May 29, 2018

Abstract

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.

First claim

What is claimed is:

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.

Assignees

• 3M Innovative Properties Co
• Univ Texas

Inventors

• Vasilakos John
• Overwijk Willem

Classifications

• A61K39/395

  Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07K16/2818

  against CD28 or CD152 · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K2039/505

  comprising antibodies · CPC title