eligibility_summary
Adults (≥18) with HER2+ (IHC3+ or 2+/ISH+) unresectable/metastatic BTC (GBC/ICC/ECC), ≤2 prior cycles of CisGem ± durvalumab/pembrolizumab, assessable disease, ECOG 0–1, adequate organs, neg pregnancy test, contraception. Exclude prior HER2 agents, other CPIs, small cell, neuroendocrine, lymphoma, sarcoma, mucinous cystic types, systemic steroids, brain mets, active infections, transplant, autoimmune disease, ILD/pneumonitis, recent trials, breastfeeding, phenytoin, other safety concerns.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 3, open-label, randomized trial in first-line advanced HER2-positive biliary tract cancer: zanidatamab + cisplatin/gemcitabine (CisGem) with or without a PD-1/L1 inhibitor (physician’s choice durvalumab or pembrolizumab) vs standard CisGem ± PD-1/L1 inhibitor. Interventions and mechanisms: Zanidatamab (ZW25, humanized IgG1 bi-epitope anti-HER2 monoclonal antibody) binds HER2 extracellular domains 2 and 4 to block signaling, drive receptor internalization, and trigger ADCC. Cisplatin (platinum cytotoxic) forms DNA crosslinks. Gemcitabine (antimetabolite nucleoside analog) inhibits DNA synthesis and ribonucleotide reductase. Pembrolizumab (anti-PD-1 IgG4) and durvalumab (anti-PD-L1 IgG1) are immune checkpoint inhibitors that enhance T-cell activity. Targets/pathways: HER2/ERBB2 on tumor cells, PD-1/PD-L1 axis on T cells/tumor, and tumor DNA replication/repair.