eligibility_summary
Inclusion: >18, HER2+ advanced breast cancer with brain mets (<15) on MRI, KPS ≥70 or ≥60 w/ neuro sx, life expectancy >6 mo, dex ≤16 mg/d, ≥2 wks since prior tx, AEs ≤G1, adequate CBC, liver/renal function, LVEF ≥50%, QTcF <480 ms, INR/APTT ≤1.5x ULN, consent. Exclusion: leptomeningeal/hemorrhagic mets, uncontrolled epilepsy, severe CV/renal/hepatic disease, immunodeficiency, active infection or transplant, drug allergy, pregnancy/lactation or no contraception, MRI inability, sponsor decision.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase II, single-arm study testing trastuzumab deruxtecan (T-DXd, DS‑8201a) plus stereotactic radiotherapy (SRT) for HER2‑positive breast cancer brain metastases. Interventions: SRT per lesion number/volume, T-DXd 5.4 mg/kg IV every 3 weeks (dose reductions allowed) starting within 2 weeks post-SRT. Mechanisms: T-DXd is an antibody–drug conjugate, the trastuzumab mAb binds HER2 (ERBB2), inhibits HER2 signaling and can trigger ADCC, then is internalized to release the DXd payload, a membrane‑permeable topoisomerase I inhibitor causing DNA damage and bystander killing. SRT delivers precise, high-dose radiation that induces DNA double-strand breaks and tumor cell death and may enhance BBB permeability and immunogenicity. Targets/pathways: HER2-overexpressing tumor cells, HER2/ERBB signaling, topoisomerase I–dependent DNA replication, and radiation-induced DNA damage/DDR pathways.