Immunotherapy Combined With Anti-angiogenic Therapy and Chemotherapy for Potentially Resectable MSI-H, dMMR Locally Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

Inclusion criteria

• Able to understand and agree to comply with study requirements and the assessment schedule, and voluntarily sign the written informed consent form (ICF) before any trial-related procedures are implemented;
• Age greater than 18 years, regardless of gender. Histologically confirmed unresectable locally advanced or metastatic G/GEJ adenocarcinoma.
• No prior systemic treatment for unresectable locally advanced or metastatic G/GEJ adenocarcinoma. Previous neoadjuvant and/or adjuvant therapy is acceptable, but all systemic treatments must have been completed at least 6 months prior to the diagnosis of unresectable or metastatic disease.
• PD-L1 combined positive score (CPS) less than 1 as determined by tissue testing.
• At least one measurable lesion according to RECIST 1.1 criteria.
• ECOG performance status 0-1.
• Life expectancy >3 months.
• Adequate organ and marrow function:

Exclusion criteria

• 1. Known HER2-positive expression (immunohistochemistry [IHC] 3+ or 2+ with a fluorescence in situ hybridization HER2:CEP17 ratio ≥2).
• Presence of other malignancies within 5 years prior to treatment, with the exception of adequately treated cervical carcinoma in situ, basal cell or squamous cell carcinoma of the skin, locally treated prostate cancer, and ductal carcinoma in situ (hormone therapy for non-metastatic prostate cancer or breast cancer is permitted).
• Known central nervous system metastases and/or carcinomatous meningitis.
• Patients with severe cardiac, pulmonary, hepatic, or renal dysfunction.
• Hypertension that cannot be controlled with antihypertensive medications (systolic blood pressure >140 mmHg, diastolic blood pressure >90 mmHg).
• History of bleeding within 4 weeks prior to screening, with any bleeding event graded as ≥3 according to CTCAE 5.0.
• Thrombotic events (arterial or venous) within 6 months prior to screening, such as cerebrovascular accident, deep vein thrombosis (excluding previously thrombosed veins deemed healed by the investigator), and pulmonary embolism.
• History of immunodeficiency, or other acquired or congenital immunodeficiency diseases, or history of organ transplantation.
• Patients who have previously received anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibodies at any time.