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

Patent metadata

Field	Value
Publication number	US-10266595-B2
Application number	US-201816213960-A
Country	US
Kind code	B2
Filing date	Dec 7, 2018
Priority date	May 15, 2012
Publication date	Apr 23, 2019
Grant date	Apr 23, 2019

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 tumor in a human subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-PD-L1 antibody; wherein the anti-PD-L1 antibody is administered intravenously over 60 minutes infusion; wherein the tumor is derived from a cancer of the ureter; and wherein the tumor is refractory to a platinum based chemotherapy.

2. The method of claim 1 , wherein the tumor is advanced.

3. The method of claim 1 , wherein the tumor is locally advanced.

4. The method of claim 1 , wherein the tumor is metastatic.

5. The method of claim 1 , wherein the therapeutically effective amount of the anti-PD-L1 antibody is administered once every 3 weeks.

6. The method of claim 1 , wherein the anti-PD-L1 antibody is formulated in a pharmaceutical composition.

7. The method of claim 6 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable salt, an anti-oxidant, an aqueous carrier, a non-aqueous carrier, or any combination thereof.

8. The method of claim 7 , wherein the salt comprises a sodium salt.

9. The method of claim 7 , wherein the salt comprises sodium chloride.

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

11. The method of claim 1 , wherein at least 5% of tumor cells exhibit membrane PD-L1 expression.

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

13. The method of claim 2 , further comprising administering an anti-cancer agent.

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

15. The method of claim 4 , further comprising administering an anti-cancer agent.

16. The method of claim 10 , further comprising administering an anti-cancer agent.

17. The method of claim 12 , wherein the anti-cancer agent is a chemotherapy.

18. The method of claim 12 , wherein the anti-cancer agent is a radiotherapy.

19. The method of claim 13 , wherein the anti-cancer agent is a chemotherapy.

20. The method of claim 13 , wherein the anti-cancer agent is a radiotherapy.

21. The method of claim 14 , wherein the anti-cancer agent is a chemotherapy.

22. The method of claim 14 , wherein the anti-cancer agent is a radiotherapy.

23. The method of claim 1 , wherein the platinum-based chemotherapy comprises cisplatin, carboplatin, or both.

24. The method of claim 1 , wherein the subject is further administered a corticosteroid.

25. A method of treating a tumor in a human subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-PD-L1 antibody once every 3 weeks;
wherein the anti-PD-L1 antibody is administered intravenously over 60 minutes infusion;
wherein the tumor is derived from a cancer of the ureter;
wherein the tumor is advanced or metastatic; and
wherein the tumor is refractory to a platinum based chemotherapy.

26. The method of claim 1 , wherein the subject is administered an antihistamine prior to the anti-PD-L1 antibody.

27. The method of claim 25 , wherein the subject is administered an antihistamine prior to the anti-PD-L1 antibody.

28. A method of treating a tumor in a human subject in need thereof, comprising administering to the subject about 10 mg/kg of an anti-PD-L1 antibody once every 2 weeks, wherein the anti-PD-L1 antibody is administered intravenously over 60 minutes infusion; wherein the tumor is derived from a cancer of the ureter; and wherein the tumor is refractory to a platinum based chemotherapy.

29. The method of claim 28 , wherein the tumor is locally advanced or metastatic.

30. The method of claim 28 , wherein at least 1% of tumor cells exhibit membrane PD-L1 expression.

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

• G01N2800/52

  Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis · CPC title

• C07K16/18

  against material from animals or humans · CPC title