eligibility_summary
Adults with stage IV/recurrent EGFR-mutant NSCLC (L858R, Ex19del, G719X, L861Q, S768I). Dose escalation: progressed on any EGFR-TKI (if T790M+, also on osimertinib). Expansion: progressed on 1L osimertinib, no non-ERBB bypass resistance, HER2-aberrant subset allowed. Needs measurable disease, post-progression tissue, ECOG 0–1, stable steroid-free brain mets, adequate organs, LVEF ≥50%. Excludes pneumonitis, leptomeningeal, major cardiac/VTE, uncontrolled CNS/HTN, strong CYP drugs, active infection, pregnancy, recent RT/chemo, prior EGFR mAb/HER2 therapy (expansion).
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase I single-arm study in EGFR-mutant metastatic/recurrent NSCLC with acquired resistance to EGFR TKIs. Interventions: Osimertinib (oral small-molecule, 3rd-generation irreversible EGFR tyrosine-kinase inhibitor selective for activating/T790M mutations), Cetuximab (IV chimeric IgG1 monoclonal antibody against EGFR that blocks ligand binding, promotes receptor downregulation, and mediates ADCC), Tucatinib (oral small-molecule, selective HER2/ERBB2 tyrosine-kinase inhibitor). Targets: EGFR-dependent tumor cells with ERBB-driven resistance, especially HER2 overexpression/amplification or mutation. Goal: shut down the ERBB network—EGFR and HER2 and their heterodimers—suppressing downstream MAPK/ERK and PI3K/AKT signaling.