2023 World Conference on Lung Cancer (Posters)-P1.12. In Vivo Efficacy of AZD9592, an EGFR-cMET Bispecific ADC, in a Broad Panel of NSCLC Patient-Derived Xenograft Models

P1.12. In Vivo Efficacy of AZD9592, an EGFR-cMET Bispecific ADC, in a Broad Panel of NSCLC Patient-Derived Xenograft Models - PDF(Abstract)

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This document is a summary of a presentation titled "In Vivo Efficacy of AZD9592, an EGFR-cMET Bispecific ADC, in a Broad Panel of NSCLC Patient-Derived Xenograft Models." The presentation was given at the WCLC 2023 conference, specifically in the session on Tumor Biology - Translational Biology - Translational Therapeutics.<br /><br />The presentation discusses the molecular mechanisms of acquired resistance to targeted therapies, such as tyrosine kinase inhibitors (TKIs), in non-small-cell lung cancer (NSCLC). The authors present a preclinical evaluation of a novel antibody-drug conjugate (ADC) called AZD9592. AZD9592 is composed of a bispecific antibody targeting epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition tyrosine kinase receptor (cMET), conjugated to a topoisomerase 1 inhibitor.<br /><br />The efficacy of AZD9592 was analyzed in 138 xenograft models derived from NSCLC patients with or without activating EGFR mutations, and who were treatment-naive or had received chemotherapy or other targeted agents. The results showed tumor regression in a majority of the models with EGFR mutations, as well as in models with atypical EGFR mutations and wild-type EGFR.<br /><br />The efficacy of AZD9592 was also observed in models previously treated with different generations of EGFR TKIs and in models treated with a combination of an EGFR TKI and a cMET TKI. Notably, models with prior exposure to an ALK TKI also showed tumor regression. EGFR wild-type models with or without prior exposure to chemotherapy also showed similar efficacy.<br /><br />Overall, the findings suggest that AZD9592 may provide clinical benefit in NSCLC patients with different molecular profiles, including those previously treated with chemotherapy or targeted agents. Additional analyses of EGFR and cMET target expression by immunohistochemistry will be presented.

Asset Subtitle

Lara McGrath

Meta Tag

Speaker Lara McGrath

Topic Tumor Biology: Translational Biology - Translational Therapeutics

Keywords

In Vivo Efficacy

AZD9592

EGFR-cMET Bispecific ADC

NSCLC Patient-Derived Xenograft Models

Molecular Mechanisms

Acquired Resistance

Tyrosine Kinase Inhibitors

Non-Small-Cell Lung Cancer

Preclinical Evaluation

Antibody-Drug Conjugate