eligibility_summary
Adults (≥18) with HER2+ metastatic solid tumors and brain mets (untreated or progressing, ≥0.5–<3 cm target, no urgent/local-therapy lesions). Measurable/evaluable extracranial disease. Prior HER2 therapy allowed (breast/gastric: ≥1 line). ECOG 0–2, life ≥3 mo, adequate labs, LVEF ≥50, contrast brain MRI, consent, contraception, biopsy if safe. Exclude: >3 cm/urgent lesions, >4 mg dex, uncontrolled seizures, recent therapy, unresolved tox, major cardiac/QTc, MI/angina, strong CYP3A/2C8 drugs, HBV/HCV/HIV, pregnancy, GI absorption issues, other cancer <1 yr, eligible for HER2CLIMB-02.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase II single-arm trial testing tucatinib plus ado-trastuzumab emtansine (T-DM1) in HER2-positive metastatic solid tumors with brain metastases. Tucatinib: oral small-molecule, highly selective HER2 (ERBB2) tyrosine kinase inhibitor that suppresses downstream PI3K/AKT and MAPK signaling and has CNS penetration. T-DM1: IV antibody–drug conjugate (trastuzumab linked via non-cleavable MCC to DM1, a maytansinoid microtubule inhibitor). T-DM1 binds HER2, blocks signaling, mediates ADCC, and delivers DM1 to disrupt microtubules causing mitotic arrest/apoptosis. Targets: HER2-overexpressing or ERBB2-mutant tumor cells and HER2-driven pathways, including in brain metastases.