eligibility_summary
Eligibility: Age 18–75, resectable HER2+ (IHC≥2+ and FISH+) esophagogastric junction adenocarcinoma (Siewert I–III), stage cT3–4a N+ M0, ECOG 0–1, life expectancy >6 mo, no prior therapy, PD-L1 not required, adequate hematologic, renal (Cr≤1.5×ULN or CrCl>60) and hepatic function, negative pregnancy test if applicable, consent. Exclude: no eval, investigator deems unfit, withdrawal, protocol violations/other anti-cancer drugs.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Trial: Perioperative therapy for HER2-positive resectable esophagogastric junction adenocarcinoma. Arms: (1) Nivolumab + FLOT + trastuzumab, then surgery, then adjuvant nivolumab + FLOT + trastuzumab, followed by maintenance nivolumab + trastuzumab vs (2) FLOT + trastuzumab throughout, then trastuzumab maintenance. Drugs and mechanisms: • Nivolumab: anti–PD-1 monoclonal antibody (immune checkpoint inhibitor) that blocks PD-1 on T cells to restore antitumor T-cell activity (PD-1/PD-L1 axis). • Trastuzumab: anti-HER2 monoclonal antibody that inhibits HER2/ERBB2 signaling and mediates ADCC against HER2+ tumor cells. • FLOT chemotherapy: docetaxel (taxane, stabilizes microtubules, blocks mitosis), oxaliplatin (platinum, DNA crosslinks), 5-fluorouracil (antimetabolite, thymidylate synthase inhibition and RNA/DNA effects), leucovorin (folate, enhances 5-FU). Targets: HER2-overexpressing tumor cells, tumor-infiltrating T cells via PD-1, DNA synthesis/repair and mitotic machinery in rapidly dividing cancer cells.