eligibility_summary
Adults (≥18) with HER2‑negative metastatic breast cancer and CNS disease. A/B: ≥1 cm measurable brain mets (new or progressing), C: evaluable leptomeningeal disease. ECOG 0–2, LVEF ≥50%, adequate organs, washouts, MRI or contrast CT (A/B). Cohort A needs prior endocrine therapy, any prior lines allowed, extracranial disease optional. Exclude visceral crisis, urgent CNS surgery/local therapy, significant bleed/≥2 seizures, uncontrolled illness, >4 mg dex, ILD, recent major surgery, corneal disease, hypersensitivity, pregnancy, contraception required.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 2, single-arm, multi-cohort trial testing datopotamab deruxtecan (Dato-DXd, DS-1062a), an antibody-drug conjugate (ADC). Mechanism: a humanized anti-TROP2 IgG1 binds TROP2 on tumor cells, is internalized, and via a cleavable linker releases the DXd payload (a membrane-permeable topoisomerase I inhibitor), causing DNA damage, replication stress, and tumor cell death with a bystander effect. Intervention: IV Dato-DXd every 21 days. Population: HER2-negative metastatic breast cancer with CNS involvement—ER+ with brain metastases, triple-negative with brain metastases, and leptomeningeal metastases. Cells/pathways targeted: TROP2-expressing breast cancer cells in CNS and leptomeninges, the topoisomerase I/DNA replication pathway within tumor cells. Aim: evaluate safety and efficacy in brain and leptomeningeal metastases.