eligibility_summary
Adults (≥18) with unresectable/metastatic NSCLC and ALK/ROS1/RET fusion (IHC/FISH/CLIA-NGS), prior progression on ≥1 approved TKI, on stable TKI ≥8 wks, measurable disease (RECIST, treated/stable brain mets allowed), ECOG 0–2, adequate organs, washouts, contraception. Exclude: prior EGFR/MET agents, rapid TKI failure (<8 wks), SCLC/neuroendocrine, active symptomatic CNS, major CV disease, ILD, GI malabsorption, active HIV/HBV/HCV, pregnancy, unresolved tox, recent surgery/vaccines/trials.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Interventions: Amivantamab (JNJ-61186372), an IV bispecific IgG1 monoclonal antibody to EGFR and MET, combined with standard small‑molecule TKIs against ALK, ROS1, or RET (e.g., ALK: alectinib/brigatinib/lorlatinib, ROS1: entrectinib/lorlatinib, RET: selpercatinib/pralsetinib). Mechanisms: Amivantamab blocks EGFR and MET ligand binding, induces receptor degradation, and triggers immune effector killing via ADCC (NK cells) and trogocytosis (macrophages). TKIs directly inhibit the driver fusion kinases ALK/ROS1/RET. Cells/pathways targeted: NSCLC tumor cells with ALK, ROS1, or RET fusions and co-expression/activation of EGFR (ERBB) and c-MET pathways. Strategy aims to prevent bypass “kinase-switch” resistance by dual EGFR/MET blockade plus ongoing ALK/ROS1/RET inhibition.