USE OF ANTI-PD-1 ANTIBODY IN COMBINATION WITH ANTI-CD27 ANTIBODY IN CANCER TREATMENT

• US 20170174774A1
• Filed: 12/19/2016
• Published: 06/22/2017
• Est. Priority Date: 12/17/2015
• Status: Active Grant

• Current Assignee: Bristol-Myers Squibb Company, Celldex Therapeutics Incorporated
• Original Assignee: Bristol-Myers Squibb Company, Celldex Therapeutics Incorporated
• Inventors: CORIC, Vladimir, Keler, Tibor, Davis, Thomas
• Granted Patent: US 10,392,442 B2
• 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: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/0008 Antigens related to auto-immune diseases; Preparations to induce self-tolerance
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/001129 Molecules with a "CD" designation not provided for elsewhere
• CPC Class Codes: A61K 39/00115 Apoptosis related proteins, e.g. survivin or livin
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• 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: 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 16/3023 Lung
• CPC Class Codes: C07K 16/3046 Stomach, Intestines
• CPC Class Codes: C07K 16/3053 Skin, nerves, brain
• CPC Class Codes: C07K 16/3069 Reproductive system, e.g. ovaria, uterus, testes, prostate
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of 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

Abstract

This invention provides methods for treating cancer in a subject comprising administering to the subject an anti-PD-1 antibody and an anti-CD27 antibody. In some embodiments, the cancer is colorectal cancer, rectal cancer, colon cancer, lung cancer, melanoma, ovarian cancer, head and neck cancer, or any combination thereof.

Claims

1. A method for treating a subject afflicted with a tumor comprising administering the subject in need thereof

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

anti-PD-1 antibody or antigen-binding portion thereof”

) in combination with

an antibody or an antigen-binding portion thereof that specifically binds to CD27 (“

anti-CD27 antibody or antigen-binding portion thereof”

).

2. The method of claim 1, wherein the tumor is colorectal cancer, rectal cancer, colon cancer, lung cancer, melanoma, ovarian cancer, head and neck cancer, or any combination thereof.

3. The method of claim 2, wherein the lung cancer is non-small cell lung cancer (NSCLC).

4. The method of claim 1, wherein the anti-PD-1 antibody or antigen-binding portion thereof cross-competes with nivolumab for binding to human PD-1.

5. The method of claim 1, wherein the anti-CD27 antibody or antigen-binding portion thereof cross-competes with varlilumab for binding to human CD27.

6. The method of claim 1, wherein:

(i) the anti-PD-1 antibody is nivolumab;

(ii) the anti-CD27 antibody is varlilumab;

or

(iii) the anti-PD-1 antibody is nivolumab and the anti-CD27 antibody is varlilumab.

7. The method of claim 1, wherein the anti-PD-1 antibody or antigen-binding portion thereof is administered at a dose ranging from at least about 0.1 mg/kg to at least about 10.0 mg/kg body weight once about every 1, 2 or 3 weeks.

8. The method of claim 7, wherein the anti-PD-1 antibody or antigen-binding portion thereof is administered at a dose of at least about 3 mg/kg body weight once about every 2 weeks.

9. The method of claim 1, wherein the anti-CD27 antibody or antigen-binding portion thereof is administered at a dose ranging from at least about 0.01 mg/kg to at least about 10 mg/kg body weight once about every 1, 2 or 3 weeks.

10. The method of claim 9, wherein the anti-CD27 antibody or antigen-binding fragment thereof is administered at a dose of 0.1 mg/kg body weight, 1 mg/kg body weight, or 10 mg/kg body weight once about every 2 weeks.

11. The method of claim 1, wherein the anti-PD-1 antibody or antigen-binding fragment thereof and the anti-CD27 antibody or antigen-binding fragment thereof are formulated for intravenous administration.

12. The method of claim 1, wherein the anti-PD-1 antibody or antigen-binding fragment thereof and the anti-CD27 antibody or antigen-binding fragment thereof are administered sequentially, concurrently in separate compositions, or concurrently as a single composition.

13. The method of claim 1, wherein:

(i) the anti-PD-1 antibody or antigen-binding portion thereof is administered at a subtherapeutic dose;

(ii) the anti-CD27 antibody or antigen-binding portion thereof is administered at a subtherapeutic dose;

or

(iii) the anti-PD-1 antibody or antigen-binding portion thereof and the anti-CD27 antibody or antigen-binding portion thereof are each administered at a subtherapeutic dose.

14. The method of claim 1, wherein the tumor is colon cancer.

15. The method of claim 14, further comprising determining the microsatellite status of the subject'"'"'s tumor.

16. The method of claim 14, wherein the subject has a microsatellite instability low (MSI-L) tumor or a microsatellite stable (MSS) tumor.

17. The method of claim 15, wherein the microsatellite status of the subject'"'"'s tumor is determined prior to treatment with the anti-PD-1 antibody or antigen-binding portion thereof in combination with the anti-CD27 antibody or antigen-binding portion thereof.

18. The method of claim 1, wherein the tumor is PD-L1 positive.

19. The method of claim 1, further comprising measuring PD-L1 expression in the tumor.

20. The method of claim 1, further comprising administering an anti-cancer agent.