METHOD OF TREATING CANCER USING IMMUNE CHECKPOINT INHIBITOR

• US 20170037132A1
• Filed: 07/14/2016
• Published: 02/09/2017
• Est. Priority Date: 07/14/2015
• Status: Active Grant

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: MANEKAS, Demetrios, Grosso, Joseph, Anderson, Jeffrey
• Granted Patent: US 10,544,224 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• 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: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/2818 against CD28 or CD152
• CPC Class Codes: C07K 16/2827 against B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/51 Complete heavy chain or Fd fragment, i.e. VH + CH1
• 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: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 1/708 for papilloma
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2333/025 Papovaviridae, e.g. papillomavirus, polyomavirus, SV40, BK virus, JC virus
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/57407 Specifically defined cancers
• CPC Class Codes: G01N 33/5743 of skin, e.g. melanoma

Abstract

This disclosure provides a method for treating HPV-positive squamous cell carcinoma of the head and neck comprising administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody or an anti-PD-L1 antibody. The disclosure also provides a method for treating HPV-negative squamous cell carcinoma of the head and neck administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody or an anti-PD-L1 antibody. The subject can be additionally administered another anti-cancer agent.

Claims

1. A method for treating a subject afflicted with a tumor derived from a human papilloma virus (HPV)-positive squamous cell carcinoma head and neck cancer (SCCHN) comprising administering to the subject a therapeutically effective amount of:

an antibody or antigen-binding portion thereof that binds specifically to a Programmed Death-1 receptor (PD-1) or Programmed Death-Ligand 1 (PD-L1) and inhibits PD-1 activity (“

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

) or PD-L1 activity (“

anti-PD-L1 antibody or antigen-binding portion thereof”

), respectively.

5. The method of claim 1, wherein the HPV-positive SCCHN comprises a tumor expressing one or more proteins derived from an HPV or a nucleotide sequence encoding the one or more proteins.

7. The method of claim 5, wherein the one or more proteins derived from an HPV comprise p16, Ki-67, Cyclin D1, p53, ProEx C, E6, E7, or any combination thereof.

11. The method of claim 1, wherein the HPV comprises HPV subtype 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, or any combination thereof.

12. The method of claim 1, wherein more than about 70% of tumor cells in the tumor show strong and diffuse nuclear and cytoplasmic staining by an immunohistochemistry against p 16.

14. The method of claim 1, wherein the tumor further expresses PD-L1.

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

16. The method of claim 1, wherein the anti-PD-1 antibody or antigen-binding portion thereof or the anti-PD-L1 antibody or antigen-binding portion thereof is a chimeric, humanized or human monoclonal antibody or a portion thereof.

17. The method of claim 1, 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.

18. The method of claim 1, wherein the anti-PD-1 antibody is nivolumab or pembrolizumab.

20. The method of claim 1, wherein the anti-PD-L1 antibody or antigen-binding portion thereof competes for binding with BMS-936559, MPDL3280A, MEDI4736 or MSB0010718C for binding to human PD-L1.

22. The method of claim 1, wherein the anti-PD-L1 antibody or antigen-binding portion thereof comprises a heavy chain constant region which is of a human IgG1 or IgG4 isotype.

23. The method of claim 1, wherein the anti-PD-L1 antibody is BMS-936559.

27. The method of claim 1, wherein the anti-PD-1 antibody or antigen-binding portion thereof or the anti-PD-L1 antibody or antigen-binding portion thereof is administered at a dose ranging from at least about 80 mg to at least about 800 mg or at least about 0.1 mg/kg to at least about 10.0 mg/kg body weight.

28. The method of claim 27, wherein the anti-PD-1 antibody or antigen-binding portion thereof or the anti-PD-L1 antibody or antigen-binding portion thereof is administered at a dose of at least about 3 mg/kg body weight or 240 mg once about every 2 weeks.

32. The method of claim 1, wherein the subject exhibits an overall survival of at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months at least about 15 months, at least about 16 months, at least about 17 months, at least about 18 months, at least about 19 months, at least about 20 months, at least about 21 months, at least about 22 months, at least about 23 months, at least about 2 years, at least about 3 years, at least about 4 years, or at least about 5 years after the administration.

35. The method of claim 1, which further comprises administering one or more additional anti-cancer agents.

36. The method of claim 35, wherein the anti-cancer agent is selected from the group consisting of (i) an antibody or antigen-binding portion thereof that binds specifically to a CTLA-4 and inhibits CTLA-4 activity, (ii) a chemotherapy, (iii) a platinum-based doublet chemotherapy, (iv) a tyrosine kinase inhibitor, (v) an anti-VEGF inhibitor, or (vi) any combination thereof.

38. A kit for treating a subject afflicted with a tumor derived from an HPV-positive SCCHN, the kit comprising:

(a) an anti-PD-1 antibody or antigen-binding portion thereof or an anti-PD-L1 antibody or antigen-binding portion thereof;

(b) instructions for determining the HPV positivity of the tumor and, if the tumor is positive for HPV, administering the anti-PD-1 antibody or antigen-binding portion thereof or the anti-PD-L1 antibody or antigen-binding portion thereof to the subject in the method of claim 1.

2. A method of treating a subject afflicted with a tumor derived from an HPV-positive SCCHN comprising:

(i) measuring a level of HPV in a sample of the subject, wherein the subject is positive for HPV; and

(ii) administering to the subject a therapeutically effective amount of an anti-PD-1 antibody or antigen-binding portion thereof or an anti-PD-L1 antibody or antigen-binding portion thereof.

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