eligibility_summary
Inclusion: ≥20, unresectable locally advanced/metastatic non‑squamous NSCLC, activating HER2 mutation by NGS (IHC any), measurable, prior platinum, ECOG 0–1, LVEF ≥50%, adequate organs, asymptomatic/stable brain mets, contraception. Exclusion: active/symptomatic brain or leptomeningeal disease, recent anti‑cancer therapy/radiation, unresolved >G2 tox, recent MI/CHF, ILD/pneumonitis, uncontrolled infection (HBV/HCV/HIV) or live vaccine, serious pulmonary disease, prior HER2 therapy except TKIs.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Intervention: Trastuzumab deruxtecan (T-DXd, DS-8201/Enhertu) 5.4 mg/kg q3w, an antibody–drug conjugate (ADC) composed of a humanized anti‑HER2 IgG1 (trastuzumab sequence), a cleavable tetrapeptide linker, and an exatecan‑derived topoisomerase I inhibitor payload. Mechanism: T‑DXd binds HER2 (ERBB2) on tumor cells, is internalized, linker is cleaved, and the payload inhibits topoisomerase I to induce DNA damage and apoptosis, also provides HER2 signaling blockade, ADCC, and a membrane‑permeable payload enabling a bystander effect. Targets: HER2‑mutant NSCLC cells (activating mutations incl. exons 19/20) including intracranial metastases. Key pathways: HER2/ERBB2 receptor signaling and DNA replication/repair via topo I inhibition. Exploratory: ILD profiling and cytokines linked to JAK/STAT.