eligibility_summary
Include: Adults ≥18 with HER2-low metastatic breast cancer and measurable brain mets (RANO-BM, ≥10 mm, ± untreated type II LMD), no immediate local therapy needed, KPS≥70/ECOG 0–2, LE ≥12 wks, ≥1 prior systemic line, LVEF≥50%, adequate organs, tox ≤G1, contraception. Exclude: prior/contraindication/allergy to T-DXd, recent therapy, other active cancer, MI/CHF, QTc>470, ILD/major lung disease, pregnant/lactating, active HBV/HCV or uncontrolled HIV, recent major surgery, CNS/psych disorder, chronic steroids, substance abuse, concurrent trial/therapy.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
NCT06048718 tests trastuzumab deruxtecan (T-DXd, DS-8201a, ENHERTU), a HER2-directed antibody-drug conjugate. Type: humanized IgG1 monoclonal antibody (trastuzumab) linked via a cleavable tetrapeptide linker to DXd, a membrane-permeable exatecan derivative/topoisomerase I inhibitor, IV 5.4 mg/kg every 3 weeks. Mechanism: the antibody binds HER2 on tumor cells (including HER2-low), is internalized, and the linker is cleaved in lysosomes to release DXd, which inhibits topoisomerase I, causing DNA damage and apoptosis, the payload’s permeability enables bystander killing. The antibody can also inhibit HER2 signaling and engage immune effector cells via ADCC. Targets: HER2-expressing breast cancer cells in brain metastases/leptomeningeal disease, HER2 signaling pathway, topoisomerase I in tumor cells, Fcγ receptor–bearing immune cells (for ADCC).