eligibility_summary
Adults 18–75 with histologically/cytologically confirmed gastric or GEJ adenocarcinoma, stage II–III (cT2–4a, N±, M0), no prior systemic therapy, HER2 IHC 2+/3+, measurable disease, ECOG 0–1, ≥6‑mo survival, adequate organs. Exclude other active cancers, PK‑affecting GI disease, prior transplant, recent systemic therapy/immunosuppression, immunodeficiency/autoimmune disease, allergy, recent thrombosis/bleeding/CV disease, serious infection, postop recovery, pregnancy/lactation or no contraception, or investigator concerns.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 2, single-arm perioperative study in HER2-overexpressing locally advanced gastric/GEJ adenocarcinoma testing: 1) Disitamab vedotin (RC48), an anti-HER2 antibody–drug conjugate delivering MMAE (microtubule inhibitor). 2) Tislelizumab, a PD-1–blocking IgG4 monoclonal antibody (checkpoint inhibitor). 3) Capecitabine, an oral prodrug of 5-fluorouracil (antimetabolite). Mechanisms: Disitamab vedotin binds HER2 on tumor cells, internalizes, and releases MMAE to disrupt tubulin, trigger G2/M arrest and apoptosis, with potential ADCC/bystander effects. Tislelizumab blocks PD-1 signaling to restore cytotoxic T-cell activity. Capecitabine→5-FU inhibits thymidylate synthase and impairs DNA/RNA synthesis. Targets: HER2 on tumor cells, microtubule polymerization, PD-1/PD-L1 immune checkpoint (T cells, tumor/APCs), and nucleotide synthesis in proliferating cancer cells.