Combination of pd-1 inhibitors and lag-3 inhibitors for enhanced efficacy in treating cancer

A technology of -LAG-3, -PD-1, applied in the field of combination of PD-1 inhibitor and LAG-3 inhibitor for enhancing potency in treating cancer

Pending Publication Date: 2021-12-21
REGENERON PHARM INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Simultaneous targeting of LAG-3 and PD-1, including in anti-PD-1 resistant tumors, may result in objective responses across multiple tumor types in patients

Method used

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  • Combination of pd-1 inhibitors and lag-3 inhibitors for enhanced efficacy in treating cancer
  • Combination of pd-1 inhibitors and lag-3 inhibitors for enhanced efficacy in treating cancer
  • Combination of pd-1 inhibitors and lag-3 inhibitors for enhanced efficacy in treating cancer

Examples

Experimental program
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preparation example Construction

[0064] Purification of antigens is generally not necessary for antibody production. Animals can be immunized with cells bearing the antigen of interest. Splenocytes can then be isolated from the immunized animal and can be fused with a myeloma cell line to generate hybridomas (see, e.g., Meyaard et al. (1997) Immunity 7:283-290; Wright et al. ( 2000) Immunity 13:233-242; Preston et al., supra; Kaithamana et al. (1999) J. Immunol. 163:5157-5164).

[0065] Antibodies can be conjugated to, eg, small drug molecules, enzymes, liposomes, polyethylene glycol (PEG). Antibodies are useful for therapeutic, diagnostic, kit, or other purposes, and include those conjugated to, for example, dyes, radioisotopes, enzymes, or metals (e.g., colloidal gold) (see, e.g., Le Doussal et al. (1991) J. Immunol. .146:169-175; Gibellini et al. (1998) J. Immunol.160:3891-3898; Hsing and Bishop (1999) J. Immunol.162:2804-2811; Everts et al. (2002) J. Immunol.168 :883-889).

[0066] Methods for flow cy...

Embodiment 1

[0142] Example 1: Clinical Trial of Anti-PD-1 Antibody and Anti-LAG-3 Antibody in Patients with Advanced Malignancy

[0143] This is a Phase 1, first-in-human (FIH), open-label, Multicenter, dose-escalation study. Study flow chart (for individual patients) such as figure 1 , and a diagram showing the study design of the dose escalation scheme and cohorts is shown in figure 2 shown.

[0144] An exemplary anti-PD-1 antibody used in this example is REGN2810 (also known as simiprimab, ). An exemplary anti-LAG2 antibody used in this example is REGN3767.

[0145] Purpose

[0146] The underlying purpose of the study was to assess safety and pharmacokinetics to determine expanded selected dose levels of REGN3767 as monotherapy and in combination with REGN2810 in patients with (advanced malignancies, including lymphoma). The underlying purpose of the dose escalation phase is to assess the preliminary antitumor activity of REGN3767 alone and in combination with REGN2810 (by co...

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PUM

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Abstract

The present disclosure provides methods for treating or inhibiting the growth of cancer comprising selecting a patient with cancer and administering a therapeutically effective amount of a LAG-3 inhibitor in combination with a therapeutically effective amount of a PD-1 inhibitor (e.g., an anti-PD-1 antibody or antigen-binding fragment thereof). In certain embodiments, the administration of the PD-1 inhibitor enhances the efficacy of a LAG-3 inhibitor (e.g., an anti-LAG-3 antibody or antigen-binding fragment thereof) in inhibiting the growth of cancer.

Description

technical field [0001] The present disclosure provides, in part, compositions comprising inhibitors of LAG-3 and PD-1 and methods for treating cancer. [0002] sequence listing [0003] An official copy of the Sequence Listing is submitted electronically via EFS-Web as the Sequence Listing in ASCII format in parallel with the description, file name 10568WO01_SEQ_LIST_ST25, date of creation May 12, 2020, and approximately 20 kilobytes in size. The Sequence Listing contained in this ASCII format file is part of the specification and is hereby incorporated by reference in its entirety. Background technique [0004] Programmed death-1 (PD-1) receptor signaling in the tumor microenvironment plays a key role in allowing tumor cells to evade the immune surveillance of the host immune system. The PD-1 receptor has two ligands, PD-ligand-1 (PD-L1) and PD-L2. Blockade of the PD-1 signaling pathway has demonstrated clinical activity in patients with multiple tumor types, and antibo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/00A61P35/00C07K16/28
CPCA61P35/00C07K16/2818C07K16/2803A61K2039/507C07K2317/76C07K2317/21A61K2039/505C07K2317/90A61K2039/545C07K16/2827A61K38/193A61K38/20A61K38/2013A61K38/2046A61K38/208A61K38/2086A61K39/04A61K39/3955C07K16/2809C07K16/2887C07K16/3092C07K2317/31
Inventor G·克鲁格T·N·西姆斯
Owner REGENERON PHARM INC
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