eligibility_summary
Inclusion: 18–75, inoperable/metastatic HER2+ (IHC 2+/3+) gastric/GEJ adenocarcinoma, measurable disease, no prior systemic therapy or relapse >6 mo post-adjuvant, ECOG 0–1, adequate organ/cardiac (LVEF≥50%), consent, contraception. Exclusion: drug allergy, major CV/cerebrovascular events or uncontrolled HTN, ILD/pulmonary disease, autoimmune/immune deficiency/HIV/transplant, serious infection/TB, CNS mets, surgery ≤28 d, GI ulcer/obstruction/perf, live vaccine ≤4 w, other serious conditions or trials
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase II, single-arm trial in first-line HER2-positive advanced gastric/GEJ adenocarcinoma tests RC48 (disitamab vedotin) + tislelizumab + S-1. RC48 is an anti-HER2 antibody-drug conjugate (humanized IgG1 linked to MMAE), it binds HER2 on tumor cells, is internalized, and releases MMAE to disrupt microtubules, causing mitotic arrest/apoptosis, with potential ADCC/bystander effects. Tislelizumab is an anti-PD-1 IgG4 checkpoint inhibitor that blocks PD-1 on T cells to restore antitumor immunity. S-1 is an oral fluoropyrimidine (tegafur/gimeracil/oteracil): tegafur → 5-FU inhibits thymidylate synthase and RNA/DNA synthesis, gimeracil inhibits DPD to increase 5-FU, oteracil reduces GI toxicity. Targets/pathways: HER2+ tumor cells, tubulin/microtubules, PD-1/PD-L1 axis on T cells, and thymidylate synthase–dependent DNA synthesis.