TREATMENT USING BRUTON'S TYROSINE KINASE INHIBITORS AND IMMUNOTHERAPY

• US 20150118222A1
• Filed: 10/24/2014
• Published: 04/30/2015
• Est. Priority Date: 10/25/2013
• Status: Abandoned Application

• Current Assignee: Pharmacyclics LLC (Abbvie Incorporated), Board of Trustees of the Leland Stanford Junior University (Stanford University)
• Original Assignee: Pharmacyclics Incorporated (Abbvie Incorporated)
• Inventors: CHANG, Betty, LEVY, Ronald, NG, Patrick, SAGIV-BARFI, Idit, KOHRT, Holbrook
• Application Number:
  US14/523,782
• Publication Number:
  US 20150118222A1
• Time in Patent Office: Days
• US Class Current: 424/130.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• 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 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 35/04 specific for metastasis
• 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
• CPC Class Codes: C07K 16/2827 against B7 molecules, e.g. CD80, CD86
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Combinations of Bruton'"'"'s tyrosine kinase (Btk) inhibitors, e.g., 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one, with immunotherapy are provided. Also provided are methods of treating cancers, and autoimmune disorders by administering combinations of Bruton'"'"'s tyrosine kinase (Btk) inhibitors, e.g., 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one, and an immune checkpoint inhibitor.

Claims

1. A method for treating a cancer comprising administering to a subject in need thereof a combination comprising a BTK inhibitor and an immune checkpoint inhibitor.

2. The method of claim 1, wherein the immune checkpoint inhibitor is an inhibitor of Programmed Death-Ligand 1 (PD-L1, also known as B7-H1, CD274), Programmed Death 1 (PD-1), CTLA-4, PD-L2 (B7-DC, CD273), LAG3, TIM3, 2B4, A2aR, B7H1, B7H3, B7H4, BTLA, CD2, CD27, CD28, CD30, CD40, CD70, CD80, CD86, CD137, CD160, CD226, CD276, DR3, GAL9, GITR, HAVCR2, HVEM, IDO1, IDO2, ICOS (inducible T cell costimulator), KIR, LAIR1, LIGHT, MARCO (macrophage receptor with collageneous structure), PS (phosphatidylserine), OX-40, SLAM, TIGHT, VISTA, VTCN1, or any combinations thereof.

3. The method of claim 2, wherein the immune checkpoint inhibitor is an inhibitor of PD-L1, PD-1, CTLA4, LAG3, or TIM3.

4. The method of claim 1, wherein the cancer is a hematologic cancer, a sarcoma, or a carcinoma.

5. The method of claim 4, wherein the cancer is selected from diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), B cell prolymphocytic leukemia (B-PLL), non-CLL/SLL lymphoma, mantle cell lymphoma, multiple myeloma, Waldenströ

m'"'"'s macroglobulinemia, bladder cancer, breast cancer, colon cancer, gastroenterological cancer, kidney cancer, lung cancer, ovarian cancer, pancreatic cancer, prostate cancer, proximal or distal bile duct cancer, melanoma, or a combination thereof.

6. The method of claim 1, wherein the cancer is a relapsed or refractory cancer, or a metastasized cancer.

7. The method of claim 1, wherein the BTK inhibitor is ibrutinib.

8. The method of claim 1, wherein the method further comprises administering an additional anticancer agent.

9. A pharmaceutical combination comprising:

a) a BTK inhibitor; and

b) an immune checkpoint inhibitor; and

c) a pharmaceutically-acceptable excipient.

10. The pharmaceutical combination of claim 9, wherein the immune checkpoint inhibitor is an inhibitor of Programmed Death-Ligand 1 (PD-L1, also known as B7-H1, CD274), Programmed Death 1 (PD-1), CTLA-4, PD-L2 (B7-DC, CD273), LAG3, TIM3, 2B4, A2aR, B7H1, B7H3, B7H4, BTLA, CD2, CD27, CD28, CD30, CD40, CD70, CD80, CD86, CD137, CD160, CD226, CD276, DR3, GAL9, GITR, HAVCR2, HVEM, IDO1, IDO2, ICOS (inducible T cell costimulator), KIR, LAIR1, LIGHT, MARCO (macrophage receptor with collageneous structure), PS (phosphatidylserine), OX-40, SLAM, TIGHT, VISTA, VTCN1, or any combinations thereof.

11. The pharmaceutical combination of claim 9, wherein the BTK inhibitor is ibrutinib.

12. The pharmaceutical combination of claim 9, further comprising an additional anticancer agent.

13. A method of treating an ibrutinib-resistant cancer comprising administering to a subject in need thereof a combination comprising ibrutinib and an immune checkpoint inhibitor.

14. The method of claim 13, wherein the immune checkpoint inhibitor is an inhibitor of Programmed Death-Ligand 1 (PD-L1, also known as B7-H1, CD274), Programmed Death 1 (PD-1), CTLA-4, PD-L2 (B7-DC, CD273), LAG3, TIM3, 2B4, A2aR, B7H1, B7H3, B7H4, BTLA, CD2, CD27, CD28, CD30, CD40, CD70, CD80, CD86, CD137, CD160, CD226, CD276, DR3, GAL9, GITR, HAVCR2, HVEM, IDO1, IDO2, ICOS (inducible T cell costimulator), KIR, LAIR1, LIGHT, MARCO (macrophage receptor with collageneous structure), PS (phosphatidylserine), OX-40, SLAM, TIGHT, VISTA, VTCN1, or any combinations thereof.

15. The method of claim 13, wherein the ibrutinib-resistant cancer is a hematologic cancer, a sarcoma, or a carcinoma.

16. The method of claim 15, wherein the ibrutinib-resistant cancer is selected from diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), B cell prolymphocytic leukemia (B-PLL), non-CLL/SLL lymphoma, mantle cell lymphoma, Waldenströ

m'"'"'s macroglobulinemia, bladder cancer, breast cancer, colon cancer, gastroenterological cancer, kidney cancer, lung cancer, ovarian cancer, pancreatic cancer, prostate cancer, proximal or distal bile duct cancer, melanoma, or a combination thereof.

17. The method of claim 13, wherein the ibrutinib-resistant cancer is a relapsed or refractory cancer, or a metastasized cancer.

18. A method for treating a cancer comprising administering to a subject in need thereof a combination comprising a BTK inhibitor and an inhibitor of PD-L1, PD-1, or CTLA-4.

19. A pharmaceutical combination comprising:

a) a BTK inhibitor; and

b) an inhibitor of PD-L1, PD-1, or CTLA-4; and

c) a pharmaceutically-acceptable excipient.

20. A method for treating an ibrutinib-resistant cancer comprising administering to a subject in need thereof a combination comprising ibrutinib and an inhibitor of PD-L1, PD-1, or CTLA-4.