Cancer immunotherapy by disrupting PD-1/PD-L1 signaling

Patent metadata

Field	Value
Publication number	US-10577423-B2
Application number	US-201916248222-A
Country	US
Kind code	B2
Filing date	Jan 15, 2019
Priority date	May 15, 2012
Publication date	Mar 3, 2020
Grant date	Mar 3, 2020

Abstract

The disclosure provides a method for immunotherapy of a subject afflicted with cancer, comprises administering to the subject a composition comprising a therapeutically effective amount of an antibody that inhibits signaling from the PD-1/PD-L1 signaling pathway. This disclosure also provides a method for immunotherapy of a subject afflicted with cancer comprising selecting a subject that is a suitable candidate for immunotherapy based on an assessment that the proportion of cells in a test tissue sample from the subject that express PD-L1 on the cell surface exceeds a predetermined threshold level, and administering a therapeutically effective amount of an anti-PD-1 antibody to the selected subject. The invention additionally provides rabbit mAbs that bind specifically to a cell surface-expressed PD-L1 antigen in a FFPE tissue sample, and an automated IHC method for assessing cell surface expression in FFPE tissues using the provided anti-PD-L1 Abs.

First claim

What is claimed is:

1. A method of treating a cancer of the head or neck in a human subject in need thereof, comprising administering to the subject an anti-PD-L1 antibody once every 3 weeks, wherein the anti-PD-L1 antibody is administered intravenously over 60 minutes infusion, wherein at least 1% of tumor cells of the cancer exhibit membrane PD-L1 expression, and wherein the subject is administered an antihistamine and an antipyretic prior to the anti-PD-L1 antibody.

2. The method of claim 1 , wherein the cancer of the head or neck is a squamous cell carcinoma of the head or neck.

3. The method of claim 1 , further comprising administering a standard of care chemotherapeutic regimen.

4. The method of claim 2 , wherein the standard of care chemotherapeutic regimen is administered prior to the anti-PD-L1 antibody.

5. The method of claim 2 , wherein the standard of care chemotherapeutic regimen comprises a platinum-based chemotherapy.

6. The method of claim 4 , wherein the platinum-based chemotherapy comprises cisplatin.

7. The method of claim 1 , further comprising administering a radiation therapy.

8. The method of claim 2 , further comprising administering cisplatin and a radiation therapy.

9. The method of claim 7 , wherein the cisplatin is administered prior to the anti-PD-L1 antibody.

10. A method of treating a cancer of the head or neck in a human subject in need thereof, comprising administering to the subject (i) a standard of care chemotherapeutic regimen and (ii) an anti-PD-L1 antibody, wherein the anti-PD-L1 antibody is administered once every 3 weeks intravenously over 60 minutes infusion.

11. The method of claim 10 , wherein the cancer of the head or neck is a squamous cell carcinoma of the head or neck.

12. The method of claim 10 , wherein the standard of care chemotherapeutic regimen is administered prior to the anti-PD-L1 antibody.

13. The method of claim 10 , wherein the standard of care chemotherapeutic regimen comprises cisplatin.

14. The method of claim 10 , further comprising administering a radiation therapy.

15. The method of claim 10 , wherein the standard of care chemotherapeutic regimen comprises cisplatin, and wherein the subject is further administered a radiation therapy.

16. The method of claim 15 , wherein the cisplatin and the radiation therapy are administered prior to the anti-PD-L1 antibody.

17. The method of claim 10 , further comprising administering an antihistamine and an antipyretic prior to the anti-PD-L1 antibody.

18. The method of claim 1 , wherein the cancer is advanced.

19. The method of claim 18 , wherein the cancer is locally advanced.

20. The method of claim 10 , wherein the cancer is advanced.

21. The method of claim 20 , wherein the cancer is locally advanced.

22. The method of claim 10 , wherein at least 1% of tumor cells of the cancer exhibit membrane PD-L1 expression.

23. A method of treating squamous cell carcinoma of the head or neck in a human subject in need thereof, comprising administering to the subject (i) a standard of care chemotherapeutic regimen and (ii) an anti-PD-L1 antibody, wherein the anti-PD-L1 antibody is administered once every 3 weeks intravenously, wherein the standard of care chemotherapeutic regimen comprises cisplatin, wherein at least 1% of tumor cells of the cancer exhibit membrane PD-L1 expression, and wherein the subject is administered an antihistamine and an antipyretic prior to the anti-PD-L1 antibody.

24. The method of claim 23 , further comprising administering a radiation therapy.

25. The method of claim 23 , wherein the squamous cell carcinoma of the head or neck is locally advanced.

26. A method of treating squamous cell carcinoma of the head or neck in a human subject in need thereof, comprising administering to the subject a combination of (i) a standard of care chemotherapeutic regimen and (ii) a pharmaceutical composition comprising an anti-PD-L1 antibody and a sodium salt, wherein the anti-PD-L1 antibody is administered intravenously over 60 minutes infusion, wherein the standard of care chemotherapeutic regimen comprises cisplatin, wherein at least 1% of tumor cells of the cancer exhibit membrane PD-L1 expression, and wherein the subject is administered an antihistamine and an antipyretic prior to the anti-PD-L1 antibody.

27. The method of claim 26 , wherein the cancer of the head or neck is a squamous cell carcinoma of the head or neck.

Assignees

• Bristol Myers Squibb Co

Inventors

• Cogswell John P
• Goldberg Stacie M
• Gupta Ashok K
• Jure-Kunkel Maria
• Wang xi-tao
• Wigginton Jon M

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K2039/507

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

• C07K16/2818 Primary

  against CD28 or CD152 · CPC title