eligibility_summary
Adults (≥18) with HER2+ unresectable LA/mBC after trastuzumab, taxane, and T-DXd, with progression/intolerance, RECIST-assessable, ECOG 0–2, adequate organ function, LVEF ≥50%. CNS mets allowed if stable or not needing urgent local therapy (timing post-WBRT/SRS/resection applies). Exclude prior eribulin for mBC, excess anthracyclines, major cardiac/QTc/MI, active HBV/HCV/HIV, pregnancy, warfarin, malabsorption, strong CYP3A4/2C8 drugs, MRI-ineligible, CNS: >2 cm untreated, >2 mg steroids, urgent local need, uncontrolled seizures.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Trial NCT05458674 tests a triple regimen in pretreated unresectable/metastatic HER2+ breast cancer: 1) Tucatinib (oral small‑molecule, highly selective HER2 tyrosine kinase inhibitor) blocks HER2 phosphorylation and downstream PI3K/AKT/MAPK signaling, it penetrates the CNS. 2) Trastuzumab (IV humanized anti‑HER2 monoclonal antibody) binds the HER2 extracellular domain to inhibit signaling and triggers antibody‑dependent cellular cytotoxicity via Fcγ receptor–bearing immune cells (e.g., NK cells). 3) Eribulin (IV cytotoxic microtubule dynamics inhibitor) halts microtubule growth, causing G2/M arrest and apoptosis, with potential vascular/EMT effects. Targets/pathways: HER2/ERBB2 on tumor cells, downstream PI3K/AKT/ERK, microtubules in proliferating cancer cells, immune effector engagement for ADCC, including activity in brain metastases.