Treatment of PD-L1-Positive Melanoma Using an Anti-PD-1 Antibody

• US 20160362489A1
• Filed: 04/28/2016
• Published: 12/15/2016
• Est. Priority Date: 04/28/2015
• Status: Abandoned Application

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: YANG, Arvin
• Application Number:
  US15/141,772
• Publication Number:
  US 20160362489A1
• Time in Patent Office: Days
• US Class Current: 1/1
• 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 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2039/55 characterised by the host/recipient, e.g. newborn with maternal antibodies
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2818 against CD28 or CD152
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• 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: G01N 2333/70532 B7 molecules, e.g. CD80, CD86
• CPC Class Codes: G01N 33/5743 of skin, e.g. melanoma

Abstract

The invention provides a method of treating a melanoma comprising (i) identifying a patient having a PD-L1 positive melanoma and (ii) administering to the patient an anti-PD-1 antibody or an antigen-binding portion thereof (“an anti-PD-1 antibody monotherapy”). The methods of the invention can extend progression-free survival for over 12 months and/or reduces the tumor size at least about 10%, about 20%, about 30%, about 40%, or about 50% compared to the tumor size prior to the administration.

Claims

1. A method for treating a melanoma tumor in a patient in need thereof comprising:

(i) identifying a patient having a PD-L1 positive melanoma tumor; and

(ii) administering to the patient an anti-PD-1 antibody or an antigen-binding portion thereof that binds specifically to a human PD-1 (“

anti-PD1 antibody monotherapy”

), wherein the patient is not administered a combination of an anti-PD-1 antibody or an antigen-binding portion thereof and an anti-CTLA-4 antibody or an antigen-binding portion thereof that binds specifically to a human CTLA-4 (“

combination therapy”

).

2. (canceled)

3. A method for treating a melanoma tumor in a patient in need thereof comprising administering to the patient an anti-PD-1 antibody or an antigen-binding portion thereof that binds specifically to a human PD-1 (“

anti-PD-1 antibody monotherapy”

), wherein the patient is not administered a combination of an anti-PD-1 antibody or an antigen-binding portion thereof and an anti-CTLA-4 antibody or an antigen-binding portion thereof that binds specifically to a human CTLA-4 (“

combination therapy”

), wherein the patient is identified as having a PD-L1 positive melanoma tumor prior to the administration.

9. The method of claim 3, wherein the patient is characterized by (i) extended progression-free survival for over 12 months following the administration, (ii) tumor size reduction at least about 10% compared to the tumor size prior to the administration, or (iii) both (i) and (ii).

15. The method of claim 3, further comprising measuring a PD-L1 expression on the melanoma tumor.

16. The method of claim 3, wherein the administration treats the melanoma tumor.

17. The method of claim 15, wherein the measuring comprises providing a test tissue sample obtained from the patient, the test tissue sample comprising tumor cells and/or tumor-infiltrating inflammatory cells.

18. The method of claim 17, wherein the measuring further comprises assessing the proportion of cells in the test tissue sample that express PD-L1 on the cell surface.

19. The method of claim 18, wherein the test tissue sample is a formalin-fixed paraffin-embedded (FPPE) tissue sample.

20. The method of claim 19, wherein the presence of PD-L1 is determined using an automated IHC assay.

21. The method of claim 20, wherein the IHC assay is performed using an anti-PD-L1 monoclonal antibody that specifically binds to the PD-L1 and wherein the anti-PD-L1 monoclonal antibody is selected from the group consisting of 28-8, 28-1, 28-12, 29-8, 5H1, and any combination thereof.

22. The method of claim 3, wherein the PD-L1 positive melanoma tumor is characterized by having at least about 5% of tumor cells showing binding to the anti-PD-L1 antibody or an antigen-binding portion thereof.

23. The method of claim 3, wherein the anti-PD-1 antibody or antigen-binding portion thereof cross-competes with nivolumab for binding to human PD-1.

24. The method of claim 3, wherein the anti-PD-1 antibody or antigen-binding portion thereof is a chimeric, humanized or human monoclonal antibody or a portion thereof.

25. The method of claim 3, wherein the anti-PD-1 antibody or antigen-binding portion thereof comprises a heavy chain constant region which is of a human IgG1 or IgG4 isotype.

26. The method of claim 3, wherein the anti-PD-1 antibody is nivolumab.

28. The method of claim 3, wherein the anti-PD-1 antibody or antigen-binding portion thereof is administered at a dose ranging from 0.1 to 10.0 mg/kg body weight once every 2, 3 or 4 weeks.

29. The method of claim 28, wherein the anti-PD-1 antibody or antigen-binding portion thereof is administered at a dose of 1 or 3 mg/kg body weight once every 3 weeks.

49. The method of claim 3, further comprising administering an anti-cancer agent.

50. A kit for treating a patient afflicted with a melanoma tumor, the kit 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; and

(b) instructions for using the anti-PD-1 antibody or the antigen-binding portion thereof in the method of claim 3.

4-8. -8. (canceled)

10-13. -13. (canceled)

14. A method for selecting a patient suitable for an anti-PD-1 antibody monotherapy comprising:

(i) identifying a patient having a PD-L1 positive melanoma tumor; and

(ii) instructing a healthcare provider to administer to the patient an anti-PD-1 antibody monotherapy.

27. (canceled)

30-48. -48. (canceled)

51. (canceled)