Cancer immunotherapy by disrupting pd-1/pd-l1 signaling

Patent metadata

Field	Value
Publication number	US-2019112376-A1
Application number	US-201816230657-A
Country	US
Kind code	A1
Filing date	Dec 21, 2018
Priority date	May 15, 2012
Publication date	Apr 18, 2019
Grant date	—

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

1 - 17 . (canceled)

18 . A method of treating a tumor derived from a metastatic non-small cell lung cancer (NSCLC) in a human subject, comprising administering to the subject a therapeutically effective amount of an anti-PD-1 antibody; wherein the anti-PD-1 antibody is administered by intravenous infusion; and wherein at least 20% of tumor cells in the tumor exhibit membrane PD-L1 expression.

19 . The method of claim 18 , wherein the therapeutically effective amount of the anti-PD-1 antibody is administered once every 3 weeks.

20 . The method of claim 18 , wherein the anti-PD-1 antibody is formulated in a pharmaceutical composition.

21 . The method of claim 20 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable salt, an adjuvant, an anti-oxidant, an aqueous carrier, a non-aqueous carrier, or any combination thereof.

22 . The method of claim 21 , wherein the salt comprises a sodium salt.

23 . The method of claim 21 , wherein the salt comprises sodium chloride.

24 . The method of claim 18 , wherein the tumor is refractory to a platinum based chemotherapy.

25 . The method of claim 24 , wherein the platinum-based chemotherapy comprises cisplatin, carboplatin, or both.

26 . The method of claim 18 , wherein the membranous PD-L1 expression on the tumor cells is measured prior to administering the anti-PD-1 antibody.

27 . The method of claim 26 , wherein the measuring comprises an immunohistochemistry.

28 . The method of claim 27 , wherein the immunohistochemistry is performed using an antibody comprising:
(a) a heavy chain (HC) complementarity determining region (CDR) 1 comprising the amino acid sequence set forth in the HC-CDR1 of SEQ ID NO: 35; (b) an HC-CDR2 comprising the amino acid sequence set forth in the HC-CDR2 of SEQ ID NO: 35; (c) an HC-CDR3 comprising the amino acid sequence set forth in the HC-CDR3 of SEQ ID NO: 35; (d) a light chain (LC) CDR1 comprising the amino acid sequence set forth in the LC-CDR1 of SEQ ID NO: 36; (e) an LC-CDR2 comprising the amino acid sequence set forth in the LC-CDR2 of SEQ ID NO: 36; and (f) an LC-CDR3 comprising the amino acid sequence set forth in the LC-CDR3 of SEQ ID NO: 36.

29 . A method of treating a tumor derived from a metastatic NSCLC in a human subject, comprising administering to the subject a therapeutically effective amount of an anti-PD-1 antibody once every 3 weeks;
wherein the anti-PD-1 antibody is administered by intravenous infusion; wherein the tumor is refractory to a platinum-based chemotherapy; and wherein at least 20% of tumor cells in the tumor exhibit membrane PD-L1 expression, as determined using an immunohistochemistry.

30 . The method of claim 29 , wherein the anti-PD-1 antibody is formulated in a pharmaceutical composition.

31 . The method of claim 30 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable salt, an adjuvant, an anti-oxidant, an aqueous carrier, a non-aqueous carrier, or any combination thereof.

32 . The method of claim 31 , wherein the salt comprises a sodium salt.

33 . The method of claim 32 , wherein the salt comprises sodium chloride.

34 . The method of claim 29 , wherein the platinum-based chemotherapy comprises cisplatin, carboplatin, or both.

35 . The method of claim 29 , wherein the immunohistochemistry is performed using an antibody comprising:
(a) a heavy chain (HC) complementarity determining region (CDR) 1 comprising the amino acid sequence set forth in the HC-CDR1 of SEQ ID NO: 35; (b) an HC-CDR2 comprising the amino acid sequence set forth in the HC-CDR2 of SEQ ID NO: 35; (c) an HC-CDR3 comprising the amino acid sequence set forth in the HC-CDR3 of SEQ ID NO: 35; (d) a light chain (LC) CDR1 comprising the amino acid sequence set forth in the LC-CDR1 of SEQ ID NO: 36; (e) an LC-CDR2 comprising the amino acid sequence set forth in the LC-CDR2 of SEQ ID NO: 36; and (f) an LC-CDR3 comprising the amino acid sequence set forth in the LC-CDR3 of SEQ ID NO: 36.

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

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61P43/00

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

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• A61K39/3955

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title