eligibility_summary
Inclusion: ≥18, ECOG 0–2, HER2+ MBC with brain mets, on 1L HP (±ET), 2L T‑DM1, or adjuvant trastuzumab/T‑DM1 with isolated CNS relapse, stable/no extracranial dz, adequate organs, LVEF ≥50, brain lesions ≥5 mm treated, limited CNS progressions, timely SRS/surgery/RT. Exclusion: prior HER2 TKIs (except adjuvant neratinib >12 mo), cardiopulmonary dz, uncontrolled TB/HBV/HCV/HIV, strong CYP interactions, CNS: steroids >2 mg dex, LMD, seizures, prior WBRT, untreated ≥5 mm, pregnant/breastfeeding, recent malignancy, investigational drug <30 d.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Interventions: addition of tucatinib to ongoing trastuzumab/pertuzumab or T‑DM1 after local brain therapy. Mechanisms/types: Tucatinib—oral, small‑molecule, highly selective HER2 tyrosine kinase inhibitor with CNS penetration, blocks HER2 phosphorylation and downstream PI3K/AKT/MAPK signaling. Trastuzumab—anti‑HER2 monoclonal antibody, inhibits HER2 signaling, induces receptor down‑regulation and antibody‑dependent cellular cytotoxicity (ADCC). Pertuzumab—anti‑HER2 monoclonal antibody targeting domain II, blocks HER2/HER3 dimerization and signaling. T‑DM1 (ado‑trastuzumab emtansine)—HER2‑targeted antibody‑drug conjugate delivering DM1 microtubule inhibitor, causing mitotic arrest/apoptosis. Targets: HER2‑overexpressing breast cancer cells (including brain metastases), HER2/HER3 dimerization, PI3K/AKT/MAPK, microtubules, engages immune effector cells via ADCC.