eligibility_summary
Eligibility: consent, tumor biopsy, unresectable/metastatic BC HER2‑low (IHC1+ or 2+/ISH−) or IHC0, never HER2+, 1–2 prior metastatic lines, HR+ with early ET or CDK4/6 failure, measurable lesion, small asymptomatic brain mets ok, ECOG 0–1, LVEF ≥50%, adequate organs, contraception, no prior anti‑HER2 (metastatic). Exclude prior ADC, cardiac/QT issues, ILD, active CNS/spinal cord, infection/immunodef (HBV/HCV/HIV), live vaccine, unresolved tox, autoimmune disease, pregnancy, pneumonectomy.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Intervention: Trastuzumab deruxtecan (T‑DXd, Enhertu, DS‑8201a), an anti‑HER2 antibody‑drug conjugate (humanized IgG1 monoclonal antibody trastuzumab linked via a cleavable linker to deruxtecan, a membrane‑permeable topoisomerase I inhibitor). Mechanism: Trastuzumab binds HER2 on tumor cells and is internalized, intracellular linker cleavage releases DXd to inhibit Topo‑I, inducing DNA damage and apoptosis, the payload’s bystander effect can kill adjacent low‑HER2 cells, the IgG1 Fc may also engage ADCC. Targets: HER2 on breast cancer cells (HER2‑low and IHC 0, both HR‑negative and HR‑positive), impacting HER2‑expressing/low cell populations and the DNA replication/repair pathway via Topo‑I inhibition.