eligibility_summary
Eligibility: Females ≥18 with HER2+ metastatic breast cancer and MRI/CT-confirmed measurable brain mets, ECOG 0–2, survival ≥3 months, adequate marrow/liver/renal labs, LVEF ≥50%, QTcF <470 ms, cohorts: new brain mets or progression after WBRT/SRS, negative pregnancy test/contraception if fertile. Exclude prior anti‑HER2 ADC, sequential pyrotinib+neratinib, extensive leptomeningeal mets, uncontrolled effusions, recent therapy/surgery, other recent cancer, serious cardiac disease, hypersensitivity, or per investigator.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Intervention: Disitamab vedotin (RC48), an anti-HER2 antibody–drug conjugate (ADC) carrying the microtubule toxin MMAE, combined with an oral pan-HER tyrosine-kinase inhibitor (either pyrotinib or neratinib). Mechanisms: Disitamab vedotin binds HER2 on tumor cells, is internalized, and releases MMAE to disrupt microtubules, causing G2/M arrest and apoptosis, the antibody may also mediate ADCC and a bystander effect. Pyrotinib and neratinib are irreversible EGFR/HER2/HER4 TKIs that block ErbB signaling and downstream PI3K/AKT/mTOR and RAS/RAF/MEK/ERK pathways, with CNS activity. Targets: HER2-overexpressing breast cancer cells (including brain metastases), ErbB receptor signaling, and tumor cell microtubules.