eligibility_summary
Eligibility: Adults ≥18 with locally advanced/metastatic NSCLC (TNM8) not suitable for curative surgery/radiotherapy, HER2 alteration (mutation/amplification/overexpression), at least 1 RECIST 1.1 measurable lesion, ECOG 0-1. Arms: 1) no prior systemic therapy, 2) on 1st-line 3rd-gen EGFR-TKI with local/oligo/slow progression and still benefiting, 3) after 1st-line 3rd-gen EGFR-TKI with extensive progression, no longer benefiting. Exclude: symptomatic CNS or meningeal mets, drug allergy, serious CV disease, ILD or radiation pneumonitis, neurologic/psychiatric disease, pregnancy/lactation, or other investigator concerns.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 2 parallel trial in HER2-altered locally advanced/metastatic NSCLC tests: 1) Disitamab vedotin (RC48), a HER2-targeted antibody–drug conjugate (humanized anti-HER2 IgG1 linked to MMAE) that binds HER2, is internalized, releases a microtubule-disrupting cytotoxin, and can mediate ADCC, combined with 2) TKIs: third-generation EGFR TKIs (osimertinib, furmonertinib, aumolertinib, mutant-selective, covalent EGFR inhibitors) or pyrotinib (irreversible pan-ERBB TKI against EGFR/HER2/HER4). Arms: (1) treatment-naive: RC48 + 3rd-gen EGFR TKI, (2) local/slow progression on 3rd-gen EGFR TKI: continue TKI + RC48, (3) extensive progression: RC48 + pyrotinib. Targets: HER2/ERBB2- and EGFR/ERBB1-driven tumor cells, ERBB signaling axis with downstream MAPK and PI3K–AKT pathways.