eligibility_summary
Adults (≥18) with KPS ≥70/ECOG ≤2, life expectancy ≥6 wks, adequate organ function, tumor tissue available, prior systemic therapy per tumor type, no immediate local therapy need, prior tox ≤1. Cohorts: 1=breast cancer (local HER2 status) with measurable brain mets (≥10 mm), 2=NSCLC with measurable brain mets (≥10 mm), 3=any solid tumor with LMD. Exclude: recent trial/tx/RT, prior anti‑HER3, hypersensitivity, major cardiac/pulmonary/ILD, pregnancy, active HBV/HCV/uncontrolled HIV, recent major surgery, high‑dose steroids.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase II single-arm trial of patritumab deruxtecan (HER3‑DXd) in metastatic breast cancer and NSCLC with active brain metastases, and solid tumors with leptomeningeal disease. Intervention: HER3‑DXd, an antibody‑drug conjugate comprising a fully human anti‑HER3 (ERBB3) IgG1 monoclonal antibody linked via a cleavable tetrapeptide to DXd, a membrane‑permeable exatecan‑derived topoisomerase I inhibitor, 5.6 mg/kg IV every 3 weeks. Mechanism: binds HER3 on tumor cells, internalizes, linker is cleaved in lysosomes, releasing DXd to induce DNA single‑strand breaks and apoptosis, bystander effect may kill adjacent cells. Targets: HER3‑expressing tumor cells in brain and leptomeningeal sites. Pathways affected: HER3/ERBB signaling (HER3 heterodimerization with HER2/EGFR), downstream PI3K/AKT and MAPK survival pathways, and DNA replication/repair via topo‑I inhibition.