eligibility_summary
Include: ≥18, HER2+ breast cancer, ≥2 prior anti‑HER2 (taxane+trastuzumab required), measurable disease, ECOG ≤1, adequate organs, LVEF ≥50%, baseline brain MRI allowing none/treated/non‑urgent mets. Exclude: >4 prior lines, prior tucatinib/vinorelbine for LA/MBC or anti‑HER2 TKI <12 mo, strong CYP3A/2C8 drugs, recent Tx/RT/surgery, MRI‑ineligible, unstable CNS disease, major cardiac disease, other cancer <3 yrs, severe allergy/GI malabsorption, HIV/HBV/HCV, serious comorbidity, pregnant/breastfeeding, use non‑hormonal contraception.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Trial tests triple therapy in HER2+ unresectable/metastatic breast cancer: 1) Trastuzumab (monoclonal antibody) binds the HER2 extracellular domain, blocks receptor dimerization/signaling, promotes receptor downregulation, and triggers antibody‑dependent cellular cytotoxicity (ADCC) via NK cells. 2) Tucatinib (oral small‑molecule HER2‑selective tyrosine kinase inhibitor) inhibits HER2 kinase activity, suppressing downstream PI3K/AKT and MAPK pathways, with limited EGFR inhibition and CNS activity. 3) Vinorelbine (vinca alkaloid chemotherapy) disrupts microtubule polymerization, causing mitotic arrest and apoptosis. Targets: HER2‑overexpressing breast cancer cells, including those with brain metastases, pathways include HER2/ERBB2 signaling (PI3K/AKT, RAS/RAF/MEK/ERK) and cell‑cycle/mitotic machinery, immune effector ADCC is engaged via trastuzumab.