Methods of treating cancer using pd-1 axis binding antagonists and mek inhibitors

a technology of pd1 axis and inhibitors, which is applied in the direction of antibody medical ingredients, drug compositions, peptides, etc., can solve the problems of refractory, exhaustion or tolerance to foreign antigens, etc., and achieve the effect of treating or delaying the progression of cancer

Inactive Publication Date: 2022-04-07
GENENTECH INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This combination therapy effectively targets resistant cancer cells by inhibiting the PD-1 axis and MEK pathway, leading to sustained tumor control and potentially prolonged treatment efficacy even after cessation of therapy.

Problems solved by technology

In the absence of co-stimulation, T-cells can become refractory to antigen stimulation, do not mount an effective immune response, and further may result in exhaustion or tolerance to foreign antigens.

Method used

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  • Methods of treating cancer using pd-1 axis binding antagonists and mek inhibitors
  • Methods of treating cancer using pd-1 axis binding antagonists and mek inhibitors
  • Methods of treating cancer using pd-1 axis binding antagonists and mek inhibitors

Examples

Experimental program
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Effect test

example 1

on Treatment with an Anti-PDL1 Antibody and a MEK Inhibitor Causes Sustained Tumor Regression in Vemurafenib-Progressing Tumors

[0388]While B-raf inhibition (such as by treatment with Vemurafenib) is effective in eliciting short-term tumor regression, resistance is frequently observed. This Example describes the finding that treatment with a combination of a PD-1 axis binding antagonist and a MEK inhibitor induces sustained tumor regression and increased progression-free survival in animals with Vemurafenib-progressing tumors. Moreover, treatment with a combination of a PD-1 axis binding antagonist and a MEK inhibitor was surprisingly superior to treatment with either agent individually.

[0389]Materials and Methods

Mouse Model

[0390]A melanoma GEM model B-rafV600E;PTENfl / fl; TyCreER was used. B-rafV600E and TyCreER alleles were as described in Dankort, D., et al Nat. Genet. 41(5):544-52 (2009). The PTEN conditional allele was as described in Lesche, R. et al. genesis 32:148-9 (2002).

Tum...

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PUM

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Abstract

The present invention describes combination treatment comprising a PD-1 axis binding antagonist and a MEK inhibitor and methods for use thereof, including methods of treating conditions where enhanced immunogenicity is desired such as increasing tumor immunogenicity for the treatment of cancer.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims the priority benefit of U.S. provisional application Ser. No. 62 / 024,988, filed Jul. 15, 2014, the contents of which are incorporated herein by reference in its entirety.SUBMISSION OF SEQUENCE LISTING ON ASCII TEXT FILE[0002]The content of the following submission on ASCII text file is incorporated herein by reference in its entirety: a computer readable form (CRF) of the Sequence Listing (file name: 146392027540SeqList.txt, date recorded: Jul. 8, 2015, size: 22 KB).BACKGROUND[0003]The provision of two distinct signals to T-cells is a widely accepted model for lymphocyte activation of resting T lymphocytes by antigen-presenting cells (APCs). Lafferty et al, Aust. J. Exp. Biol. Med. ScL 53: 27-42 (1975). This model further provides for the discrimination of self from non-self and immune tolerance. Bretscher et al, Science 169: 1042-1049 (1970); Bretscher, P. A., P.N.A.S. USA 96: 185-190 (1999); Jenkins et al, J. Exp...

Claims

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Application Information

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Patent Type & AuthorityApplications(United States)
IPC IPC(8): A61K39/395C07K16/28A61K31/4523
CPCA61K39/3955C07K16/2827A61K39/39558A61K31/4523A61K2039/505C07K2317/73C07K2317/72C07K2317/52C07K16/2803A61K45/06A61K2300/00C07K2317/76A61P35/00A61P35/04A61P43/00A61K2039/542C07K2317/56A61K39/395
InventorJUNTTILA, MELISSA
OwnerGENENTECH INC