eligibility_summary
Eligibility: ≥18, HER2+ unresectable/metastatic breast adenocarcinoma, ≤1 prior line (trastuzumab ± pertuzumab + taxane) or relapse ≤6 mo after (neo)adjuvant trastuzumab+taxane, progression, RECIST‑measurable or evaluable lytic/mixed bone‑only, ECOG 0–1, LVEF ≥50%, adequate organs, treated/inactive brain mets allowed, contraception/pregnancy tests. Exclude: prior anti‑HER2 ADC, cardiac disease, ILD/serious lung disease, active CNS mets, active infection, HIV/active HBV/HCV, live vaccine <30d, recent cancers.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Interventions: Trastuzumab deruxtecan (T-DXd), a HER2-targeted antibody–drug conjugate (humanized anti‑HER2 monoclonal antibody linked via a cleavable linker to DXd, a membrane‑permeable topoisomerase I inhibitor), dosed 5.4 mg/kg IV q3w, plus a liquid-biopsy companion diagnostic (HER2‑2D) and serial ctDNA NGS. Mechanisms: T-DXd binds HER2, is internalized, releases DXd to inhibit topoisomerase I, causing DNA damage and bystander killing. Targets/pathways: HER2/ERBB2-expressing breast cancer cells (including HER2-low), payload targets topoisomerase I. Liquid biopsy tracks HER2 amplification/overexpression and resistance mechanisms involving PI3K/AKT (PIK3CA), PTEN loss, integrin signaling, YAP1, and IGF1 pathways.