COMBINATIONS OF CHECKPOINT INHIBITORS AND THERAPEUTICS TO TREAT CANCER

• US 20150202291A1
• Filed: 11/05/2014
• Published: 07/23/2015
• Est. Priority Date: 11/05/2013
• Status: Abandoned Application

• Current Assignee: Cognate BioServices, Inc., Northwest Biotherapeutics Incorporated, Revimmune, Inc, Regents of the University of California (University of California)
• Original Assignee: Cognate BioServices, Inc., Northwest Biotherapeutics Incorporated, Revimmune, Inc, Regents of the University of California (University of California)
• Inventors: Liau, Linda M., Bosch, Marnix Leo, Ganjel, James Kelly, Powers, Linda F., Prins, Robert M.
• Application Number:
  US14/534,158
• Publication Number:
  US 20150202291A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61F 7/00 Heating or cooling appliances for medical or therapeutic treatment of the human body heating or cooling means in connection with bedsteads or mattresses A47C21/00 ; massage, therapeutic baths A61H; hyperthermia using electric or magnetic fields or ultrasound A61N; electric heating elements H05B
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2039/55516 Proteins; Peptides
• CPC Class Codes: A61K 2039/55527 Interleukins
• CPC Class Codes: A61K 2239/31 characterized by the route of administration
• CPC Class Codes: A61K 2239/38 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2239/47 Brain; Nervous system
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 35/15 Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells presenting a specific antigen A61K39/00; therapeutic combinations of antibodies, or fragments thereof, and blood-derived cells A61K39/00
• CPC Class Codes: A61K 38/20 Interleukins [IL]
• CPC Class Codes: A61K 38/2046 IL-7
• CPC Class Codes: A61K 38/2086 IL-13 to IL-16
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 39/4615 Dendritic cells
• CPC Class Codes: A61K 39/4622 Antigen presenting cells
• CPC Class Codes: A61K 39/464499 Undefined tumor antigens, e.g. tumor lysate or antigens targeted by cells isolated from tumor
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61N 5/10 : X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy A61N5/01 takes precedence
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 37/04 : Immunostimulants
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/2818 : against CD28 or CD152

Abstract

A combination treatment regimen including one or more cycles and/or doses of a checkpoint inhibitor and a therapeutic, either sequentially, in either order, or substantially simultaneously, can be more effective in treating cancer in some subjects and/or can initiate, enable, increase, enhance or prolong the activity and/or number of immune cells, the efficacy of anti-tumor immune responses or a medically beneficial response by a tumor.

Claims

1. A method of treating cancer or initiating, enhancing, or prolonging an anti-tumor response in a subject in need thereof comprising administering to the subject a therapeutic agent in combination or a combined treatment regimen with an agent that is a checkpoint inhibitor.

2. The method of claim 1, wherein the checkpoint inhibitor is a biologic therapeutic or a small molecule.

3. The method of claim 1, wherein the checkpoint inhibitor is selected from the group consisting of a monoclonal antibody, a humanized antibody, a fully human antibody and a fusion protein or a combination thereof.

4. The method of claim 1, wherein the checkpoint inhibitor inhibits a checkpoint protein selected from the group consisting of CTLA-4, PDL1, PDL2, PD1, B7-H3, B7-H4, BMA, HVEM, TIM3, GAL9, LAG3, VISTA, KIR, 2B4, CD160, CGEN-15049, CHK 1, CHK2, A2aR, and B-7 family ligands or a combination thereof.

5. The method of claim 1, wherein the checkpoint inhibitor interacts with a ligand of a checkpoint protein selected from the group consisting of CTLA-4, PDL1, PDL2, PD1, B7-H3, B7-H4, BTLA, HVEM, TIM3, GAL9, LAG3, VISTA, KIR, 2B4, CD160, CGEN-15049, CHK 1, CHK2, A2aR, and B-7 family ligands or a combination thereof.

6. The method of claim 1, wherein the therapeutic agent is selected from the group consisting of an immunostimulatory agent, a T cell growth factor, an interleukin, an antibody and a vaccine or a combination thereof.

7. The method of claim 6, wherein the interleukin is IL-7 or IL-15.

8. The method of claim 7, wherein the interleukin is glycosylated IL-7.

9. The method of claim 6, wherein the vaccine is a dendritic cell vaccine.

10. The method of claim 1, wherein the checkpoint inhibitor and the therapeutic are administered simultaneously or sequentially in either order.

11. The method of claim 10, wherein the therapeutic is administered prior to the checkpoint inhibitor.

12. The method of claim 11, wherein the therapeutic is a vaccine and the checkpoint inhibitor is a PD-1 inhibitor or a CTLA-4 inhibitor.

13. The method of claim 10, wherein the vaccine is a dendritic cell vaccine.

14. The method of claim 1, wherein treatment is determined by a clinical outcome;

an increase, enhancement or prolongation of anti-tumor activity by T cells;

an increase in the number of anti-tumor T cells or activated T cells as compared with the number prior to treatment or a combination thereof.

15. The method of claim 14, wherein clinical outcome is selected from the group consisting of tumor stabilization tumor regression;

tumor shrinkage;

tumor necrosis;

anti-tumor response by the immune system;

by tumor expansion, recurrence or spread or a combination thereof.

16. The method of claim 1, wherein the treatment effect is predicted by presence or status of T cells or by presence of a gene signature indicating T cell infiltration or inflammation or a combination thereof.

17. The method of claim 1, wherein the subject has cancer.

18. The method of claim 17, wherein the cancer is selected from the group consisting of urogenital, gynecological, lung, gastrointestinal, head and neck cancer, brain cancers including malignant gliomas and brain metastases, malignant mesothelioma, non-metastatic or metastatic breast cancer, malignant melanoma, Merkel Cell Carcinoma or bone and soft tissue sarcomas, haematologic neoplasias, multiple myeloma, acute myelogenous leukemia, chronic myelogenous leukemia, myelodysplastic syndrome and acute lymphoblastic leukemia, non-small cell lung cancer (NSCLC), breast cancer, metastatic colorectal cancers, hormone sensitive or hormone refractory prostate cancer, colorectal cancer, ovarian cancer, hepatocellular cancer, renal cell cancer, pancreatic cancer, gastric cancer, oesophageal cancers, hepatocellular cancers, cholangiocellular cancers, head and neck squamous cell cancer soft tissue sarcoma, and small cell lung cancer.

19. The method of claim 1, further comprising administering a chemotherapeutic agent, targeted therapy, radiation, cryotherapy or hyperthermia therapy to the subject either prior to, simultaneously with, or after treatment with the combination therapy.

20. A method of enhancing or prolonging the effects of a checkpoint inhibitor, or enabling a subject to respond to a checkpoint inhibitor, or enabling the toxicity or the dose or number of treatments of a checkpoint inhibitor to be reduced, comprising administering to a subject in need thereof a therapeutic in combination with a checkpoint inhibitor.

21. The method of claim 20, wherein the checkpoint inhibitor is a biologic therapeutic or a small molecule.

22. The method of claim 20, wherein the checkpoint inhibitor is selected from the group consisting of a monoclonal antibody, a humanized antibody, a fully human antibody and a fusion protein or a combination thereof.

23. The method of claim 20, wherein the checkpoint inhibitor inhibits a checkpoint protein selected from the group consisting of CTLA-4, PDL1, PDL2, PD1, B7-H3, B7-H4, BTLA, HVEM, TIM3, GAL9, LAG3, VISTA, KIR, 2B4, CD160, CGEN-15049, CHK 1, CHK2, A2aR, and B-7 family ligands or a combination thereof.

24. The method of claim 20, wherein the checkpoint inhibitor interacts with a ligand of a checkpoint protein selected from the group consisting of CTLA-4, PDLL, PDL2, PD1, B7-H3, B7-H4, BTLA, HVEM, TIM3, GAL9, LAG3, VISTA, KIR, 2B4, CD160, CGEN-15049, CHK 1, CHK2, A2aR, and B-7 family ligands or a combination thereof.

25. The method of claim 20, wherein the therapeutic is selected from the group consisting of an immunostimulatory agent, a T cell growth factor, an interleukin, an antibody and a vaccine or a combination thereof.

26. The method of claim 25, wherein the interleukin is IL-7 or IL-15.

27. The method of claim 26, wherein the interleukin is glycosylated IL-7.

28. The method of claim 25, wherein the vaccine is a dendritic cell vaccine.

29. The method of claim 20, wherein the checkpoint inhibitor and the biologic therapeutic are administered simultaneously or sequentially in either order.

30. The method of claim 29, wherein the therapeutic is administered prior to the checkpoint inhibitor.

31. The method of claim 30, wherein the therapeutic is a vaccine and the checkpoint inhibitor is a PD-1 inhibitor.

32. The method of claim 29, wherein the vaccine is a dendritic cell vaccine.

33. The method of claim 20, wherein the subject has cancer.

34. The method of claim 33, wherein the cancer is selected from the group consisting of urogenital, gynecological, lung, gastrointestinal, head and neck cancer, brain cancers including malignant gliomas and brain metastases, malignant mesothelioma, non-metastatic or metastatic breast cancer, malignant melanoma, Merkel Cell Carcinoma or bone and soft tissue sarcomas, haematologic neoplasias, multiple myeloma, acute myelogenous leukemia, chronic myelogenous leukemia, myelodysplastic syndrome and acute lymphoblastic leukemia, non-small cell lung cancer (NSCLC), breast cancer, metastatic colorectal cancers, hormone sensitive or hormone refractory prostate cancer, colorectal cancer, ovarian cancer, hepatocellular cancer, renal cell cancer, pancreatic cancer, gastric cancer, oesophageal cancers, hepatocellular cancers, cholangiocellular cancers, head and neck squamous cell cancer soft tissue sarcoma, and small cell lung cancer.

35. The method of claim 20, further comprising administering a chemotherapeutic agent, targeted therapy or radiation to the subject either prior to, simultaneously with, or after treatment with the combination therapy.

37. The composition of claim 35, wherein the biologic therapeutic is a vaccine.

36. A pharmaceutical composition comprising a checkpoint inhibitor in combination with a biologic therapeutic.

38. A pharmaceutical composition comprising a dendritic cell vaccine and a PD-1 inhibitor or CTLA-4 inhibitor.

39. A combination therapy for the treatment of cancer wherein the combination therapy comprises adoptive T cell or NK cell therapy and a checkpoint inhibitor.

40. The combination therapy of claim 39, wherein the adoptive T cell therapy comprises autologous T-cells.

41. The combination therapy of claim 40, wherein the autologous T-cells are targeted against tumor antigens.

42. The combination therapy of claim 39, wherein the adoptive T cell therapy comprises allogeneic T-cells.

43. The combination therapy of claim 40, wherein the allogeneicT-cells are targeted against tumor antigens.

44. The combination therapy of claim 39, wherein the checkpoint inhibitor is a PD-1 or a PDL-1 or CTLA-4 checkpoint inhibitor.

45. A method of enhancing an anti-tumor or anti-cancer immune response, the method comprising administering to a subject adoptive T cell or NK cell therapy and a checkpoint inhibitor.

46. The method of claim 45, wherein the adoptive T cell or NK cell therapy is administered before the checkpoint inhibitor.

47. The method of claim 46, wherein the adoptive T cell or NK cell therapy is administered 1-30 days before the checkpoint inhibitor.

48. The method of claim 45, wherein the anti-tumor response is selected from inhibiting tumor growth, inducing tumor cell death, tumor regression, preventing or delaying tumor recurrence, tumor growth, tumor spread and tumor elimination.

49. A method of enhancing or prolonging the effects of a cancer vaccine, or doptive T cell or NK cell therapy, comprising administering to a subject in need thereof a sheckpoint inhibitor in combination with such vaccine or T cell or NK cell therapy.