Methods for treating metastatic triple negative breast cancer with anti-pd-1 antibodies

Patent metadata

Field	Value
Publication number	US-2022380469-A1
Application number	US-202017762215-A
Country	US
Kind code	A1
Filing date	Sep 23, 2020
Priority date	Sep 27, 2019
Publication date	Dec 1, 2022
Grant date	—

Abstract

The present invention relates to methods for treating metastatic triple negative breast cancer in a human patient which has been identified as having a PD-L1 enriched tumor comprising administering, as monotherapy, an anti-PD-1 antibody or antigen binding fragment thereof (e.g., pembrolizumab) in specific amounts to the patient about every three or six weeks, wherein the PD-L1 enriched tumor is a tumor identified as having a CPS score of ≥10.

First claim

1 . A method of treating metastatic triple negative breast cancer (mTNBC) in a human patient identified as having a PD-L1 enriched tumor, the method comprising administering to the patient, as monotherapy, an anti-PD1 antibody, or antigen binding fragment thereof, wherein the PD-L1 enriched tumor is a tumor identified as having a combined positive score (CPS) of ≥10 before the anti-PD1 antibody is administered.

2 . The method of claim 1 , wherein the anti-PD-1 antibody or antigen-binding fragment thereof comprises:
(a) light chain complementarity determining regions (CDRs) comprising a sequence of amino acids as set forth in SEQ ID NOs: 1, 2 and 3 and heavy chain CDRs comprising a sequence of amino acids as set forth in SEQ ID NOs: 6, 7 and 8; or (b) light chain CDRs comprising a sequence of amino acids as set forth in SEQ ID NOs: 11, 12 and 13 and heavy chain CDRs comprising a sequence of amino acids as set forth in SEQ ID NOs: 14, 15 and 16.

3 . The method of claim 2 , wherein the anti-PD-1 antibody or antigen-binding fragment thereof comprises:
(a) a heavy chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:9, or a variant of SEQ ID NO:9, and (b) a light chain variable region comprising: (i) a sequence of amino acids as set forth in SEQ ID NO:4, or a variant of SEQ ID NO:4, (ii) a sequence of amino acids as set forth in SEQ ID NO:22, or a variant of SEQ ID NO:22, or (iii) a sequence of amino acids as set forth in SEQ ID NO:23, or a variant of SEQ ID NO:23.

4 . The method of claim 3 , wherein the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:9 and a light chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:4.

5 . The method of claim 4 , wherein the anti-PD-1 antibody or antigen-binding fragment thereof is a monoclonal antibody comprising:
(a) a heavy chain comprising a sequence of amino acids as set forth in SEQ ID NO:10, or a variant of SEQ ID NO:10, and (b) a light chain comprising a sequence of amino acids as set forth in SEQ ID NO:5, a variant of SEQ ID NO:5, SEQ ID NO:24, a variant of SEQ ID NO:24, SEQ ID NO:25, or a variant of SEQ ID NO:25.

6 . The method of claim 1 , wherein the anti-PD-1 antibody or antigen-binding fragment thereof is a monoclonal antibody comprising a heavy chain comprising a sequence of amino acids as set forth in SEQ ID NO:10 and a light chain comprising a sequence of amino acids as set forth in SEQ ID NO: 5.

7 . The method of claim 1 , wherein the patient has received at least one prior systemic treatment for mTNBC.

8 . The method of claim 7 , wherein the patient has received at least two prior systemic treatments for mTNBC.

9 . The method of claim 7 , wherein the patient has disease progression following the at least one prior systemic treatment.

10 . The method of claim 7 , wherein the at least one prior systemic treatment comprises treatment with an anthracycline and/or a taxane in the neoadjuvant, adjuvant, or metastatic setting.

11 . The method of claim 1 , wherein the PD-L1 enriched tumor is a tumor identified as having a CPS of ≥20.

12 . The method of claim 1 , wherein the anti-PD-1 antibody or antigen-binding fragment thereof is administered to the patient by intravenous or subcutaneous administration.

13 . The method of claim 1 , wherein the anti-PD-1 antibody or antigen-binding fragment thereof is pembrolizumab.

14 . The method of claim 1 , wherein the method comprises administering:
(i) about 200 mg of an anti-PD-1 antibody, or antigen binding fragment thereof, to the patient every approximately three weeks; or (ii) about 400 mg of an anti-PD-1 antibody, or antigen binding fragment thereof, to the patient every approximately six weeks.

15 . The method of claim 8 , wherein the patient has disease progression following the at least two prior systemic treatments.

16 . The method of claim 8 , wherein the at least two prior systemic treatments comprise treatment with an anthracycline and/or a taxane in the neoadjuvant, adjuvant, or metastatic setting.

Assignees

• Merck Sharp & Dohme

Inventors

• Aktan Gursel
• Dansey Roger Delemere
• Karantza Vassiliki
• Guo Zifang
• Mejia Jaime A
• Su Shu-Chih
• Zhao Jing
• Zhou Xuan

Classifications

• A61K2039/545

  characterised by the dose, timing or administration schedule · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K16/2818 Primary

  against CD28 or CD152 · CPC title