TREATMENT OF CANCER USING A COMBINATION OF AN ANTI-PD-1 ANTIBODY AND AN ANTI-CD137 ANTIBODY

• US 20170247455A1
• Filed: 08/21/2015
• Published: 08/31/2017
• Est. Priority Date: 08/22/2014
• Status: Abandoned Application

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: JURE-KUNKEL, Maria, Berman, David M., Korman, Alan J., Selby, Mark J., Krishnan, Suba
• Application Number:
  US15/505,299
• Publication Number:
  US 20170247455A1
• Time in Patent Office: Days
• 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 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: C07K 16/2818 against CD28 or CD152
• CPC Class Codes: C07K 16/2878 against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
• CPC Class Codes: C07K 16/3061 Blood cells
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/74 Inducing cell proliferation
• CPC Class Codes: C07K 2317/75 Agonist effect on antigen
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2317/94 Stability, e.g. half-life, pH, temperature or enzyme-resistance

Abstract

This disclosure provides a method for treating a subject afflicted with a cancer, which method comprises administering to the subject therapeutically effective amounts of: (a) an antibody or an antigen-binding portion thereof that specifically binds to PD-1; and (b) an antibody or an antigen-binding portion thereof that specifically binds to CD137.

Claims

1. A method for treating a subject afflicted with a cancer, comprising administering to the subject a combination of therapeutically effective amounts of:

(a) a monoclonal antibody or an antigen-binding portion thereof that binds specifically to a Programmed Death-1 (PD-1) receptor; and

(b) a monoclonal antibody or an antigen-binding portion thereof that binds specifically to CD137.

2. The method of claim 1, wherein the cancer is a solid tumor.

3. The method of claim 2, wherein the solid tumor is selected from melanoma, prostate cancer, non-small cell lung cancer, colorectal cancer, head and neck squamous cell carcinoma, renal cell carcinoma, gastric carcinoma, glioblastoma, and Non-Hodgkin'"'"'s Lymphoma.

4. The method of claim 1, wherein the cancer is a B cell lymphoma.

5. The method of claim 4, wherein the cancer is a B-cell non-Hodgkin'"'"'s lymphoma.

6. The method of claim 1, wherein the anti-PD-1 antibody cross-competes with nivolumab for binding to human PD-1.

7. The method of claim 1, wherein the anti-PD-1 antibody is a chimeric, humanized or human monoclonal antibody or a portion thereof.

8. The method of any one of claims 1-7, wherein the anti-PD-1 antibody comprises a heavy chain constant region which is of a human IgG1, IgG2, IgG4 isotype, or variant thereof.

9. The method of claim 1, wherein the anti-PD-1 antibody is nivolumab.

10. The method of claim 1, wherein the anti-PD-1 antibody is administered at a dose of 1 or 3 mg/kg body weight once every 2 weeks.

11. The method of claim 1, wherein the anti-CD137 antibody cross-competes with urelumab for binding to human CD137.

13. The method of claim 1, wherein the anti-CD137 antibody comprises a heavy chain constant region which is of a human IgG1, IgG2, or IgG4 isotype.

14. The method of claim 1, wherein the anti-CD137 antibody is urelumab.

15. The method of claim 1, wherein the anti-CD137 antibody is administered at a dose of 3 or 8 mg once every 4 weeks.

16. The method of claim 1, wherein the method comprises at least one treatment cycle of eight weeks.

17. The method of claim 16, wherein the anti-PD-1 antibody is administered on Days 1, 15, 29, and 43 of each cycle.

18. The method of claim 16, wherein the anti-CD137 antibody is administered on Days 1 and 29 of each cycle or Day 1 of each cycle.

19. A kit for treating a subject afflicted with a cancer, comprising:

(a) a dosage ranging from 0.1 to 10 mg/kg body weight of an anti-PD-1 antibody or an antigen-binding portion thereof;

(b) a dosage ranging from 1 to 10 mg of an anti-CD137 antibody or an antigen-binding portion thereof; and

(c) instructions for using the anti-PD-1 antibody and the anti-CD137 antibody in the method of any of claims 1-38.

20. The method according to claim 1, wherein the anti-CD137 antibody binds to an CD137 epitope that either crosslinking and/or promotes Fc receptor engagement and results in CD137 agonism.

12. The method of claim 12, wherein the anti-CD137 antibody is a chimeric, humanized or human monoclonal antibody or a portion thereof.