eligibility_summary
Adults (≥18) with unresectable/metastatic invasive breast cancer, HER2-low or -0 (never HER2+), any HR, measurable disease, biopsies if accessible. HR+ must have prior endocrine incl. CDK4/6. Chemo: ADC1 0–1 prior lines, ADC2 1–2 and progression on the alternate ADC. ECOG 0–1, adequate organs, LVEF ≥50% for T-DXd, stable/treated CNS OK. Exclude: prior topo I (except per ADC2), ILD/pneumonitis, serious cardiac/corneal disease, QTc prolongation, live vaccine <30d, major surgery <2w, uncontrolled infection, pregnancy, contraception required.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase II, open-label, non-comparative trial in metastatic HER2-negative (HER2-low/0) breast cancer testing sequential antibody–drug conjugates: trastuzumab deruxtecan (T-DXd, HER2-directed ADC) and datopotamab deruxtecan (Dato-DXd, TROP2-directed ADC). Both are IgG1 monoclonal antibodies linked by a cleavable linker to the deruxtecan (DXd) topoisomerase I inhibitor payload. Mechanism: antigen binding (HER2 or TROP2) → internalization → lysosomal release of DXd → TOP1 inhibition leading to DNA damage/replication stress and tumor cell death, membrane-permeable payload may cause a bystander effect. T-DXd’s trastuzumab also blocks HER2 signaling and can mediate ADCC. Targets: HER2-expressing (including HER2-low) tumor cells, TROP2-positive tumor cells, and the TOP1/DNA replication pathway. The study evaluates efficacy of switching ADC targets after progression, in HR+ and HR− cohorts.