eligibility_summary
Eligibility: Adults with unresectable locally advanced/metastatic NSCLC, HER2 exon 20 insertion, measurable disease, ECOG 0–1, adequate organs, survival ≥12 wks, archival tissue, prior platinum and immunotherapy, consent and contraception required. Exclude: other drivers, prior HER2 therapy, major surgery <4 wks, active HBV/HCV/HIV, recent live vaccine, NYHA III HF, active infection, uncontrolled HTN/DM, ILD or COPD, systemic autoimmune therapy within 2 yrs.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Trial: NCT05745740 (Phase Ib/II). Interventions: RC48-ADC (disitamab vedotin) plus pyrotinib. RC48-ADC is a HER2-directed antibody–drug conjugate (humanized anti‑HER2 IgG1 linked to the microtubule poison MMAE). Mechanism: binds HER2 on tumor cells, internalizes, releases MMAE to disrupt microtubules causing mitotic arrest/apoptosis, may also mediate ADCC and bystander killing. Pyrotinib is an oral, irreversible pan‑ErbB small‑molecule TKI (EGFR/HER1, HER2, HER4) that covalently inhibits kinase activity, shutting down HER2/ErbB signaling and downstream PI3K/AKT and MAPK pathways. Targets: NSCLC cells harboring HER2 exon 20 insertions, HER2/ErbB signaling network and microtubules in tumor cells. Rationale: dual HER2 targeting—signal blockade plus cytotoxic delivery—to enhance antitumor efficacy.