eligibility_summary
Eligibility: Adults (≥20) with confirmed HER2+ biliary tract cancer, measurable disease, ECOG 0–1, life ≥3 mo, adequate labs/organ function, EF ≥50%, biopsy tissue, contraception. Must be untreated advanced/metastatic or recurrent >6 mo post adjuvant (≤1 gemcitabine cycle allowed). Exclude prior PD‑1/CTLA‑4, autoimmune/ILD, active infection/viral hepatitis, symptomatic brain mets/effusions, significant CV/CNS disease, uncontrolled comorbidities, recent therapy/surgery/steroids, pregnancy, Nivolumab allergy.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
NCT05749900 (HERBOT) is a multicenter, open-label, single-arm Phase Ib/II first-line trial in advanced HER2-positive biliary tract cancer testing: • Trastuzumab (humanized IgG1 anti-HER2 mAb): blocks ERBB2/HER2 signaling and induces ADCC against HER2-amplified tumor cells. • Nivolumab (human IgG4 anti–PD-1 mAb): releases PD-1 checkpoint inhibition on T cells to restore antitumor activity. • Gemcitabine (antimetabolite nucleoside analog): inhibits DNA synthesis. • Cisplatin (platinum alkylating-like agent): forms DNA crosslinks causing apoptosis. Targets/pathways: HER2/ERBB2-driven signaling (PI3K/AKT and MAPK) in tumor cells, PD-1/PD-L1 axis on tumor-infiltrating T cells, DNA replication/repair in rapidly dividing cancer cells, with potential immunogenic cell death to enhance ICI efficacy.