eligibility_summary
Eligibility: Adults with HER2+ unresectable/metastatic breast cancer after T‑DXd progression/intolerance, measurable disease, eligible for eribulin/gemcitabine/vinorelbine/capecitabine, adequate labs (incl CrCl ≥30), LVEF ≥50, ECOG 0–1. Exclude: leptomeningeal or major cardiac disease, inability to take trastuzumab, unresolved ≥G2 toxicity, infection (incl HIV, active HBV/HCV/COVID), hypersensitivity to study drugs, recent anticancer therapy or major surgery, pregnancy/breastfeeding.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 3 randomized, open-label study in metastatic HER2-positive breast cancer post–trastuzumab deruxtecan compares zanidatamab + physician’s-choice chemotherapy (eribulin, vinorelbine, gemcitabine, or capecitabine) vs trastuzumab + the same chemo options. Zanidatamab: biparatopic bispecific anti-HER2 IgG1 monoclonal antibody binding two non-overlapping epitopes (HER2 domains II and IV), blocks HER2 dimerization and signaling, promotes receptor internalization/downregulation, and triggers Fc-mediated ADCC. Trastuzumab: anti-HER2 IgG1 mAb binding domain IV, inhibits signaling and mediates ADCC. Chemotherapies: eribulin and vinorelbine (microtubule inhibitors), gemcitabine (nucleoside analog antimetabolite), capecitabine (oral 5-FU prodrug, thymidylate synthase inhibition). Targets/pathways: HER2/ERBB2→PI3K/AKT and MAPK, microtubule dynamics/mitosis, DNA synthesis, engages NK cells via FcγR for ADCC.