eligibility_summary
Adults (≥18) with HER2+ (ASCO/CAP) unresectable/metastatic breast cancer, prior taxane, trastuzumab, pertuzumab, and an ADC, progressed/intolerant, tissue for PD‑L1, ECOG 0–1, measurable disease, brain mets per protocol, LVEF ≥50%, adequate labs, contraception. Exclude prior PD‑1/PD‑L1/CTLA‑4, recent lapatinib/neratinib/afatinib, leptomeningeal disease, significant cardiac/autoimmune/infection, ILD, pregnancy, recent therapy, unresolved AEs, high steroids, QTc ≥450, warfarin, drug/vaccine interactions.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase II study in pretreated HER2-positive metastatic breast cancer (incl. brain metastases). Interventions: tucatinib (Tukysa)—oral small-molecule HER2-selective tyrosine kinase inhibitor that blocks ERBB2 signaling (PI3K/AKT, MAPK) with CNS activity, trastuzumab (Herceptin)—humanized anti-HER2 monoclonal antibody that binds extracellular HER2, inhibits signaling and mediates ADCC, pembrolizumab (Keytruda)—humanized anti-PD-1 immune checkpoint inhibitor that restores antitumor T-cell activity. Early PD-L1–negative/unknown cohort also received capecitabine (Xeloda)—oral prodrug of 5-FU antimetabolite inhibiting thymidylate synthase, later omitted due to liver test abnormalities. Targets/cells: HER2-overexpressing tumor cells and ERBB2-driven pathways, PD-1/PD-L1 axis on T cells and tumor microenvironment, engages TILs and NK cells (via trastuzumab-mediated ADCC), addresses CNS metastases.