This study was designed to explore the efficacy and safety of fruquintinib combined with tislelizumab and FOLFOX regimen as the first treatment (first-line) for adults diagnosed with locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Inclusion Criteria:

• 18-75 years old (including 18 and 75 years old);
• Eastern Cooperation Oncology Group (ECOG) performance status of 0-1;
• Pathologically determined gastric or gastroesophageal junction adenocarcinoma;
• Advanced patients with radiographic confirmation of inoperable complete resection;
• No previous anti-tumor treatment for metastatic diseases;
• At least one measurable lesion according to RECIST version 1.1;
• Ability to take medications orally;
• No active bleeding;
• Adequate organ functions:

Absolute neutrophil count ≥2×109/L; Platelet ≥100×109/L; Hemoglobin ≥90g/L; WBC≥4×109/L Total bilirubin ≤ 1.5XULN; ALT and AST ≤2.5XULN ； Serum creatinine (Cr) ≤1.5XULN；

• Have fully understood the study and voluntarily signed the informed consent;

Exclusion Criteria:

• Patients who had received any drug in the study protocol in the last year;
• Deficient mismatch repair (dMMR) or MSI-H detected by genetic test;
• HER2 positive（HER-2 3+, or HER-2 2+ and FISH+）;
• Hypertension that could not be controlled by drugs before enrollment was defined as: systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥90 mmHg;
• Patients with acute coronary syndromes (including myocardial infarction and unstable angina) received coronary angioplasty or stenting within 6 months before enrollment;
• Patients with massive pleural or peritoneal effusion requiring drainage;
• Patients with severe ECG abnormalities or heart diseases (such as cardiac insufficiency, myocardial infarction, angina pectoris) that affect clinical treatment;
• Severe lung diseases (such as interstitial pneumonia, pulmonary fibrosis, severe emphysema, etc.);
• Mental disorders or central nervous system diseases or brain metastases affecting clinical treatment;
• Patients with autoimmune diseases;
• Patients with grade 3 or higher bleeding within 4 weeks;
• Patients with a history of allergy to any drug, similar drug or vehicle in this study;
• Had a major surgical procedure (thoracotomy, or laparotomy , etc.) within 4 weeks prior to the first dose of study therapy;
• Patients with nonhealed wounds, ulcers, or fractures;
• Patients who required systemic corticosteroids (excluding temporary testing, prophylactic administration for anaphylaxis), or immunosuppressive agents or had received such agents within 14 days before enrollment;
• Pregnant or lactating women, or patients of childbearing age who refused contraception during the study period;
• Investigators believe that the patient has any other conditions that are not suitable for participating in the study.