eligibility_summary
Inclusion: adults 18–75 with unresectable locally advanced/metastatic HER2+ gastric/GEJ adenocarcinoma, RECIST 1.1–measurable disease, no prior systemic therapy or relapse >6 mo after (neo)adjuvant, ECOG 0–1, adequate organs, life ≥3 mo. Exclusion: severe drug allergy, uncontrolled CV/cerebrovascular, ILD/pneumonitis, uncontrolled systemic disease, immune disorders incl HIV or transplant, active infection incl TB, CNS mets, significant effusions, other cancer <5y, major surgery <28d.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase II randomized trial in first-line HER2+ advanced gastric/GEJ cancer. Experimental: disitamab vedotin (RC48, anti-HER2 antibody–drug conjugate delivering MMAE, a microtubule inhibitor), sintilimab (anti–PD-1 IgG4 checkpoint inhibitor), and S-1 (oral fluoropyrimidine: tegafur/gimeracil/oteracil → 5-FU). Comparator: trastuzumab (anti-HER2 monoclonal antibody) + chemotherapy (XELOX/FP/XP: capecitabine or 5-FU with oxaliplatin or cisplatin) ± sintilimab. Targets/pathways: HER2/ERBB2 on tumor cells (blocking signaling and ADC internalization, affects PI3K/MAPK and can induce ADCC), PD-1 on T cells (restores antitumor immunity), microtubules (MMAE), thymidylate synthase and RNA/DNA synthesis (5-FU/S-1/capecitabine), and DNA crosslinking/repair pathways (platinum agents).