Combination cancer therapies

Patent metadata

Field	Value
Publication number	US-2018169230-A1
Application number	US-201615577382-A
Country	US
Kind code	A1
Filing date	May 27, 2016
Priority date	May 29, 2015
Publication date	Jun 21, 2018
Grant date	—

Abstract

The disclosure provides methods of treatment for cancer in patients using bispecific anti-IGF-1R, anti-ErbB3 antibodies in combination with one or more therapeutic agents that impede regulatory T-cell agents. In certain embodiments, said one or more therapeutic agent may be an antagonistic anti-receptor antibody that immunospecifically binds human PD-L1.

First claim

What is claimed is:

1 . The use of a therapeutically effective amount of istiratumab in combination with an immunomodulatory agent to treat cancer in a human patient, where the immunomodulatory agent is selected from the group consisting of: (a) an agonistic anti-receptor antibody that immunospecifically binds human OX40, CD40, GITR, CD27, ICOS, or 4-1BB; (b) an antagonistic anti-receptor antibody that immunospecifically binds human CTLA-4, PD-1, PD-L1, TIM-3, BTLA, VISTA, LAG-3, KIR, CD47, CD25, B7-H3, or B7-H4; and (c) an anti-ligand antibody that blocks function of IL-6, IL-10, TGFβ, angiopoetin-2, VEGF, IL-17, IL-23, or TNFα.

2 . The use of claim 1 , wherein the cancer is selected from the group consisting of: colorectal cancer, melanoma, B-cell lymphoma and fibrosarcoma.

3 . The use of claim 1 or 2 , wherein the human patient does not have detectable free IGF-1 in serum prior to administration of the istiratumab to treat the cancer.

4 . The use of any one of claims 1 - 3 , wherein the PD-1 blocking antibody is nivolumab.

5 . The use of any one of claims 1 - 4 , wherein the cancer is melanoma.

6 . The use of any one of claims 1 - 5 , wherein the human patient does not have an active autoimmune condition prior to the administration of the istiratumab.

7 . The use of any one of claims 1 - 6 , wherein the istiratumab is administered once every two weeks to treat the cancer in the human patient.

8 . The use of any one of claims 1 - 7 , wherein the istiratumab is administered at a dose of 40 mg/kg or 2.8 g once every two weeks.

9 . The use of any one of claims 1 - 8 , wherein the PD-1 blocking antibody is administered once every 2 weeks at a dose of 3 mg/kg.

10 . The use of any one of claims 1 - 3 and 5 - 8 , wherein the anti-CTLA-4 antibody is ipilimumab or tremelimumab.

11 . The use of any one of claims 1 - 9 , wherein the anti-PD-1 antibody is selected from the group consisting of nivolumab, pembrolizumab, and pidilizumab.

12 . The use of any one of claims 1 - 3 and 5 - 8 , wherein the anti-PD-L1 antibody is selected from the group consisting of atezolizumab, durvalumab, and avelumab.

13 . The use of claim 12 , wherein the anti-PD-L1 antibody is atezolizumab.

14 . The use of any one of claims 1 - 3 and 5 - 8 , wherein the immunomodulatory agent is lirilumab.

15 . The use of any one of claims 1 - 3 , 5 - 8 , and 10 , wherein immunomodulatory agent is an anti-CTLA-4 antibody, and the cancer is melanoma.

16 . The use of a therapeutically effective amount of istiratumab as an immune-oncology monotherapy to treat colorectal cancer, melanoma, B-cell lymphoma or fibrosarcoma cancer in a human patient without a diagnosed active autoimmune condition.

17 . The use of claim 16 , wherein the human patient has immune cells expressing IGF-1R and ErbB3.

18 . The use of any one of claims 15 - 17 , wherein the therapeutically effective amount of istiratumab is administered once every week or once every two weeks.

19 . The use of any one of claims 15 - 18 , wherein the therapeutically effective amount of istiratumab is a fixed dose of 2.8 g, 2.24 g, or 1.96 g or 40 mg/kg administered once every two weeks.

20 . The use of an antineoplastic therapy consisting of a therapeutically effective amount of istiratumab in combination with an immunomodulatory agent selected from the group consisting of: an anti-PD-L1 antibody, an anti-CTLA-4 antibody and an anti-PD-1 antibody, to treat colorectal cancer, melanoma, B-cell lymphoma or fibrosarcoma cancer in a human patient having immune cells expressing IGF-1R and ErbB3 and without a diagnosed active autoimmune condition.

21 . The use of claim 20 , wherein the human patient has Treg cells expressing IGF-1R and ErbB3.

22 . The use of claim 20 or 21 , wherein the therapeutically effective amount of istiratumab is administered once every week or once every two weeks.

23 . The use of any one of claims 20 - 22 , wherein the therapeutically effective amount of istiratumab is a fixed dose of 2.8 g, 2.24 g, or 1.96 g or 40 mg/kg administered once every two weeks.

24 . The use of any one of claims 16 - 23 , wherein the patient has cancer cells that do not express at least one of IGF-1R and ErbB3.

25 . The use of a therapeutically effective amount of istiratumab as an immune-oncology to treat a cancer that does not express at least one of IGF-1R and ErbB3 in a human patient without a diagnosed active autoimmune condition, and having immune cells expressing IGF-1R and ErbB3.

26 . The use of claim 16 , wherein the cancer is selected from the group consisting of: colorectal cancer, melanoma, B-cell lymphoma and fibrosarcoma cancer.

27 . The use of any one of claims 24 - 26 , wherein the therapeutically effective amount of istiratumab is administered as a monotherapy, without another immunomodulatory agent, once every week or once every two weeks.

28 . The use of claim 27 , wherein the therapeutically effective amount of istiratumab is a fixed dose of 2.8 g, 2.24 g, or 1.96 g or 40 mg/kg administered once every two weeks.

29 . The use of an antineoplastic therapy consisting of istiratumab in combination with an immunomodulatory agent selected from the group consisting of: an anti-PD-L1 antibody, an anti-CTLA-4 antibody and an anti-PD-1 antibody, to treat a cancer that does not express at least one of IGF-1R and ErbB3 in a human patient without a diagnosed active autoimmune condition, and having immune cells expressing IGF-1R and ErbB3 in a human patient without a diagnosed active autoimmune condition.

30 . The use of claim 29 , wherein the cancer is selected from the group consisting of: colorectal cancer, melanoma, B-cell lymphoma and fibrosarcoma cancer.

31 . The use of claim 29 or 30 , wherein the therapeutically effective amount of istiratumab is administered as an antineoplastic therapy consisting of istiratumab and the immunomodulatory agent, once every week or once every two weeks.

32 . The use of claim 31 , wherein the therapeutically effective amount of istiratumab is a fixed dose of 2.8 g, 2.24 g, or 1.96 g or 40 mg/kg administered once every two weeks.

Assignees

• Merrimack Pharmaceuticals Inc

Inventors

• Adams Sharlene
• Curley Michael
• Finn Gregory J
• Louis Chrystal U
• Lugovskoy Alexey Alexandrovich

Classifications

• A61K2039/507

  Comprising a combination of two or more separate antibodies · CPC title

• C07K16/2827 Primary

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

• C07K16/2863

  against receptors for growth factors, growth regulators · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07K16/32

  against translation products of oncogenes · CPC title