eligibility_summary
Include: 18–75, unresectable/metastatic gastric or GEJ adenocarcinoma, PD‑L1 known, HER2+: cohorts 1–2, HER2‑low: cohort 3, no prior systemic therapy, measurable disease, ECOG 0–1, adequate organ function, survival ≥3 mo. Exclude: HER2‑neg/non‑adenoca, active CNS mets, serious GI events or absorption issues, symptomatic effusions/ascites, IBD, pregnancy, prior ICIs/ADCs or immunosuppression, ILD/pneumonitis, active infection (HBV/HCV/HIV), unresolved AEs, chemo contraindications.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase I/II, open-label trial in first-line HER2-expressing gastric/GEJ cancer. Regimens: (1) Cadonilimab (AK104, tetravalent bispecific anti–PD-1/CTLA-4 monoclonal antibody) + trastuzumab (anti-HER2 monoclonal antibody) + XELOX, (2–3) Cadonilimab + disitamab vedotin/RC48 (anti-HER2 antibody-drug conjugate delivering MMAE) + chemotherapy (mFOLFOX6, maintenance AK104+RC48+5-FU). Mechanisms: Cadonilimab dual checkpoint blockade activates effector T cells and diminishes Treg suppression, trastuzumab blocks HER2 signaling and induces ADCC, RC48 binds HER2, internalizes, and releases MMAE to disrupt microtubules (bystander effect possible), oxaliplatin crosslinks DNA, 5-FU/capecitabine inhibit thymidylate synthase (leucovorin enhances 5-FU). Targets: PD-1 and CTLA-4 on T cells, HER2 on tumor cells, microtubules, DNA synthesis/repair pathways.