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 Clinical relevance and translatability of NSCLC patient-derived xenograft (PDX) models for evaluating cMET-targeted therapies   

One of the key challenges in evaluating next-generation therapies for NSCLC is the lack of preclinical models that accurately preserve the molecular complexity and resistance mechanisms of patient tumors. Resistance to EGFR-targeted TKIs often involves c-MET amplification, underscoring the need for models that replicate this biology. Antibody-drug conjugates (ADCs) targeting c-MET, like Teliso-V, show potential, but robust translational systems are required to assess their efficacy across heterogeneous tumor types.

Champions Oncology developed low-passage NSCLC patient-derived xenograft (PDX) models that maintain the clonal architecture and mutational landscape of the original tumors, making them highly translatable for preclinical evaluation.

• In vivo studies demonstrated dose-dependent responses to a c-MET-targeting ADC across EGFR wildtype and mutant PDX models, with efficacy observed even in models resistant to osimertinib.

• Deep genomic profiling revealed distinct EGFR mutations (e.g., Ex19Del, L858R, T790M) and MET copy number variations that influenced therapeutic response and resistance patterns.

• The dataset supports the utility of Champions’ NSCLC PDX models for screening targeted therapies and guiding patient stratification in the clinic, offering a valuable platform to predict ADC efficacy in EGFR inhibitor-progressed tumors.