eligibility_summary
Incl: 18–75, gastric/GEJ adenocarcinoma, locally advanced (AJCC8 cT3–4N+M0), resectable, no prior anti‑cancer therapy, HER2 IHC 1+/2+/3+, ECOG 0–1, OS ≥6 mo, contraception, neg pregnancy, not lactating. Excl: other malignancy ≤5 y, bleeding risk/transfusion <4 w, no oral intake, trial drugs <4 w, prior anti‑HER2/PD‑(L)1/CTLA‑4, immunomodulators/TCM <2 w, active autoimmune ≤2 y or recent steroids/immunosuppression, allergy, neuropathy ≥G2, HIV/HBV/HCV active, live vaccine <30 d, PI discretion.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase II single-arm neoadjuvant trial for HER2-expressing locally advanced gastric adenocarcinoma testing short-course IMRT (25 Gy/5 fractions) followed by disitamab vedotin + S-1 + sintilimab. Disitamab vedotin: anti-HER2 antibody-drug conjugate (ADC) delivering MMAE, binds HER2 on tumor cells, internalizes, releases microtubule inhibitor to cause cell-cycle arrest/apoptosis and may trigger ADCC. S-1: oral fluoropyrimidine (tegafur/gimeracil/oteracil), prodrug of 5-FU inhibiting thymidylate synthase and RNA/DNA synthesis in proliferating tumor cells. Sintilimab: anti-PD-1 IgG4 monoclonal antibody restoring antitumor T-cell activity by blocking PD-1/PD-L1 signaling. Radiotherapy induces DNA double-strand breaks and immunogenic cell death. Targets: HER2+ tumor cells, microtubules, thymidylate synthase/DNA synthesis pathways, and PD-1 on T cells.