Combination therapy of bromodomain inhibitors and checkpoint blockade

Patent metadata

Field	Value
Publication number	US-2019192532-A1
Application number	US-201615764131-A
Country	US
Kind code	A1
Filing date	Sep 30, 2016
Priority date	Oct 2, 2015
Publication date	Jun 27, 2019
Grant date	—

Abstract

The present disclosure provides combination therapy of a bromodomain inhibitor and an immune modulator (e.g., an immune check point inhibitor). The combination of the bromodomain inhibitor and the immune modulator may be useful in treating or preventing cancer in a subject. In certain embodiments, the subject has an intact immune system. The combination of the bromodomain inhibitor and the immune modulator is expected to be synergistic.

First claim

1 . A method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of:
a bromodomain inhibitor; and, an immune modulator,
wherein the bromodomain inhibitor is a compound represented by the following structural formula

or a pharmaceutically acceptable salt thereof.

2 - 5 . (canceled)

6 . The method of claim 1 , wherein the cancer is a hematological cancer or a solid organ tumor.

7 . The method of claim 6 , wherein the hematological cancer is lymphoma, leukemia, or myeloma.

8 . The method of claim 6 , wherein the solid organ tumor is a liver, colon, breast, kidney, head and neck, melanoma, skin, pancreas, lung, prostate, or brain tumor.

9 - 37 . (canceled)

38 . The method of claim 1 , wherein the immune modulator is an immune checkpoint inhibitor.

39 . The method of claim 1 , wherein the immune checkpoint inhibitor is an inhibitor of an immune checkpoint protein selected from the group consisting of: CTLA-4, PD-1, PDL-1, TIM3, LAG3, B7-H3, B7-H4, BTLA, GAL9, and A2aR.

40 . (canceled)

41 . (canceled)

42 . The method of claim 39 , wherein the immune checkpoint inhibitor is an inhibitor of PDL-1.

43 - 53 . (canceled)

54 . The method of claim 1 , wherein the bromodomain inhibitor and the immune modulator are administered to the subject simultaneously as a single composition.

55 . The method of claim 1 , wherein the bromodomain inhibitor and the immune modulator are administered to the subject separately.

56 . The method of claim 1 , wherein the bromodomain inhibitor and the immune modulator are administered to the subject concurrently.

57 . The method of claim 56 , wherein the bromodomain inhibitor is administered to the subject after the immune modulator.

58 . The method of claim 56 , wherein the bromodomain inhibitor is administered to the subject prior to the immune modulator.

59 . The method of claim 58 , wherein the administration of the bromodomain inhibitor occurs at least 24 hours (1 day), 2 days, 3 days or 4 days prior to the administration of the immune modulator.

60 . (canceled)

61 . The method of claim 1 , wherein the subject has an intact immune system.

62 . The method of claim 1 , wherein the subject is a human.

63 . The method of claim 1 , wherein the immune modulator is the anti-PD-L1 antibody is MPDL3280A.

64 . The method of claim 1 , wherein the bromodomain inhibitor is a compound represented by the following structural formula:

or a pharmaceutically acceptable salt thereof.

65 . The method of claim 6 , wherein the cancer is a solid organ tumor selected from an ovarian cancer.

66 . The method of claim 6 , wherein the cancer is a hematological cancer selected from acute lymphocytic leukemia (ALL), acute myelocytic leukemia (AML), chronic myelocytic leukemia (CML), Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), mantle cell lymphoma (MCL), B-cell lymphoma, and multiple myeloma.

67 . The method of claim 1 , wherein the immune modulator is an anti-PD-1 antibody or an anti-4-1BB antibody.

Assignees

• Dana Farber Cancer Inst Inc
• Peter Maccallum Cancer Inst

Inventors

• Bradner James E
• Hogg Simon John
• Johnstone Ricky Wayne
• Shortt Jake

Classifications

• A61K2039/505

  comprising antibodies · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/551 Primary

  having two nitrogen atoms, e.g. dilazep · CPC title

• C07K16/2827

  against B7 molecules, e.g. CD80, CD86 · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title