Treatment of T cell lymphoma

Patent metadata

Field	Value
Publication number	US-12448442-B2
Application number	US-202117381418-A
Country	US
Kind code	B2
Filing date	Jul 21, 2021
Priority date	Jan 22, 2019
Publication date	Oct 21, 2025
Grant date	Oct 21, 2025

Abstract

The present invention relates to methods for the treatment of T cell lymphomas using compounds that specifically bind KIR3DL2 in combination with chemotherapeutic agents, notably gemcitabine and/or oxaliplatin. The treatments are particularly useful in the treatment of peripheral T cell lymphomas, for example PTCL-NOS.

First claim

We claim:

1. A method for treating a T-cell lymphoma (TCL) in an individual, the method comprising administering to the individual an antibody that binds a KIR3DL2 polypeptide in combination with gemcitabine and oxaliplatin, wherein the antibody comprises the heavy chain CDR1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 32 and the light chain CDR1, 2 and 3 of the light chain variable region of SEQ ID NO: 33.

2. The method of claim 1 , wherein gemcitabine is administered at a dose of 800-1000 mg/m 2 once every two weeks.

3. The method of claim 1 , wherein oxaliplatin is administered at a dose of 75-100 mg/m 2 once every two weeks.

4. The method of claim 1 , wherein oxaliplatin is administered at a dose of 75-130 mg/m 2 once every three weeks.

5. The method of claim 1 , wherein the antibody is administered from once per week to once every four weeks.

6. The method of claim 1 , wherein the antibody that binds KIR3DL2 polypeptide is administered once per week or the antibody is administered once per week in a first phase followed by a second phase in which the antibody is administered once every two weeks or once per month.

7. The method of claim 6 , wherein the antibody is administered at a dose of 1-20 mg/kg or at a flat dose of 750 mg.

8. The method of claim 1 , wherein the TCL is a peripheral T cell lymphoma (PTCL), adult T cell leukemia (ATL), enteropathy associated T cell lymphoma (EATL), PTCL-NOS or anaplastic large cell lymphoma (ALCL).

9. The method of claim 1 , said method further comprising a step of
a) determining the KIR3DL2 polypeptide status of malignant cells within the individual having a TCL, and
b) upon a determination that the individual has KIR3DL2 polypeptide expressed on the surface of malignant cells, administering to the individual the antibody that binds a KIR3DL2 polypeptide in combination with oxaliplatin and gemcitabine.

10. The method of claim 9 , wherein determining whether a KIR3DL2 polypeptide that is expressed on the surface of said malignant cells comprises obtaining from the individual a biological sample that comprises peripheral T cell lymphoma cells, bringing said cells into contact with an antibody that binds a KIR3DL2 polypeptide, and detecting cells expressing KIR3DL2.

11. The method of claim 1 , wherein the antibody that has reduced binding to a KIR3DL2 polypeptide having a mutation at residues 160 and/or residue G62, compared to a wild-type KIR3DL2 polypeptide of SEQ ID NO: 1.

12. The method of claim 1 , wherein gemcitabine is administered at a dose of 800-1000 mg/m 2 on days 1 and 8 of a 3 week cycle.

Assignees

• Innate Pharma

Inventors

• Abdelazim Hatem
• Paturel Carine

Classifications

• G01N33/57505

  of the blood, e.g. leukaemia · CPC title

• G01N2333/70503

  Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3 · CPC title

• C07K2317/732

  Antibody-dependent cellular cytotoxicity [ADCC] · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• A61K39/39558

  against tumor tissues, cells, antigens · CPC title