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(Slides)

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The study presented at the 2023 World Conference on Lung Cancer (WCLC) evaluated the in vivo efficacy of AZD9592, a bispecific antibody-drug conjugate (ADC), in a broad panel of patient-derived xenograft (PDX) models of non-small-cell lung cancer (NSCLC). The molecular mechanisms of acquired resistance to targeted therapies, such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), often involve aberrations in the mesenchymal-epithelial transition tyrosine kinase receptor (cMET). EGFR and cMET co-expression is common in NSCLC, making them ideal targets for anticancer therapies.<br /><br />AZD9592 is an ADC composed of a bispecific monoclonal antibody (mAb) targeting EGFR and cMET conjugated to a topoisomerase 1 inhibitor (TOP1i). It has been engineered to have reduced affinity for EGFR to mitigate EGFR-driven toxicity.<br /><br />The study found that AZD9592 showed antitumor activity in PDX models with various molecular profiles, including EGFR wild-type and mutant tumors with different mutations. The response to AZD9592 was observed regardless of prior treatment with EGFR TKIs, chemotherapy, or MET TKIs.<br /><br />Translational analyses included the characterization of somatic tumor alterations, EGFR and cMET protein expression, and correlations with prior treatments received by patients. These analyses supported the efficacy of AZD9592 in a wide range of NSCLC molecular profiles.<br /><br />The study concluded that AZD9592 may provide clinical benefit in areas of unmet need, including in patients who have previously received chemotherapy or targeted agents. Clinical investigation of AZD9592 is ongoing in a Phase 1 study evaluating its efficacy as monotherapy or in combination with other anticancer agents in patients with advanced solid tumors.<br /><br />Overall, the results of this preclinical study support further investigation of AZD9592 as a potential therapeutic option for patients with NSCLC.

Asset Subtitle

Lara McGrath

Meta Tag

Speaker Lara McGrath

Topic Tumor Biology: Translational Biology - Translational Therapeutics

Keywords

2023 World Conference on Lung Cancer

AZD9592

bispecific antibody-drug conjugate

patient-derived xenograft models

non-small-cell lung cancer

molecular mechanisms

epidermal growth factor receptor

tyrosine kinase inhibitors

mesenchymal-epithelial transition tyrosine kinase receptor

anticancer therapies