eligibility_summary
Eligibility: Adults ≥18, ECOG 0–1, HER2+ unresectable/metastatic recurrent breast cancer (HR any), relapse ≤12 mo after (neo)adjuvant anti‑HER2, measurable disease, LVEF ≥50%, adequate organ/lab function, negative pregnancy test. Exclude: prior metastatic chemo/HER2, ineligible for T‑DXd, active CNS or ILD, lung/cardiac disease, HIV/HBV/HCV, recent anti‑cancer therapy/surgery/radiation/live vaccine, prior T‑DXd or trastuzumab allergy, pregnancy, uncontrolled illness/substance abuse.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Trial: NCT05744375 (TRANSCENDER). Intervention: Trastuzumab deruxtecan (T-DXd, Enhertu), an antibody–drug conjugate (ADC). Mechanism of action: The trastuzumab (humanized anti‑HER2 IgG1) antibody binds HER2 on tumor cells and is internalized, a cleavable linker releases the DXd payload (a topoisomerase I inhibitor), which induces DNA damage and cell death. The membrane‑permeable payload enables a bystander effect. The trastuzumab component also inhibits HER2 signaling and can mediate ADCC. Cells/pathways targeted: HER2‑overexpressing breast cancer cells, ERBB2/HER2 signaling, DNA replication via TOP1. Population: First‑line therapy for HER2‑positive locally advanced/metastatic breast cancer with early relapse after (neo)adjuvant trastuzumab+pertuzumab+taxane. Note: Trial was terminated early due to insufficient accrual.