eligibility_summary
Inclusion: HER2+ esophageal/gastric/GEJ adenocarcinoma, measurable disease, ECOG 0–1, LVEF ≥53% (borderline per cardiology), adequate organs, stable treated brain mets, contraception/negative pregnancy. Prior therapy: none for metastatic, adjuvant >6 mo, maintenance nivolumab >3 mo. Exclusion: active CNS mets, autoimmune needing systemic tx ≤2y, immunodeficiency/chronic steroids, pneumonitis, infection, neuropathy >G1, cardiac disease/QTc, chronic diarrhea, recent COVID-19, pregnant/lactating.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
NCT06109467 (Phase II, single-arm) tests neratinib + trastuzumab + pembrolizumab + mFOLFOX (oxaliplatin, 5-FU/leucovorin) in HER2-overexpressing gastroesophageal adenocarcinoma. Neratinib: oral irreversible pan-HER tyrosine kinase inhibitor blocking EGFR/HER2/HER4 and downstream PI3K-AKT and MAPK pathways. Trastuzumab: anti-HER2 IgG1 monoclonal antibody inhibiting HER2 signaling/dimerization and mediating ADCC. Pembrolizumab: anti-PD-1 immune checkpoint monoclonal antibody restoring T-cell antitumor activity. Oxaliplatin: platinum cytotoxic causing DNA crosslinks. 5-FU (potentiated by leucovorin): antimetabolite inhibiting thymidylate synthase and RNA/DNA synthesis. Targets: HER2-amplified tumor cells, ERBB/HER signaling, DNA replication/repair in cancer cells, PD-1 on T cells, Fc-mediated NK-cell ADCC.