The trial is a prospective, randomized, controlled phase Ⅱ study which will be conducted in Chinese PLA General Hospital, Beijing, China. Patients with eligibility will enrolled and assigned into either group A for 9 weeks of nivolumab, S-1 combined with oxaliplatin (Nivo+SOX) followed by D2 surgery and group B for 9 weeks of nivolumab followed by D2 surgery. The primary endpoint is the safety assessed by recording adverse events and the secondary endpoints are response rate, disease control rate, pathological complete response rate, D2 rate and R0 rate.

Inclusion Criteria:

• Non-bedridden, aged 18 to 70 years old;
• Eastern Cooperative Oncology Group (ECOG) score is 0 to 1;
• Histologically confirmed gastric adenocarcinoma;
• Have evaluable lesions based on RECIST 1.1;
• Stage III (cT3-4aN1-3 M0, American Joint Committee on Cancer (AJCC) TNM staging system 8th edition) gastric cancer confirmed by enhanced computer tomography (enhanced CT) and laparoscopic exploration (endoscopic ultrasonography (EUS) and magnetic resonance imaging (MRI) if necessary);
• The surgeon have the ability to complete standard D2 radical gastrectomy and the gastrectomy can be tolerated by the patient;
• Laboratory test criteria: peripheral blood hemoglobin (Hb) ≥ 90 g/L, neutrophil absolute count ≥ 3× 109 /L, platelet count (PLT) ≥ 100× 109 /L, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal (ULN), total bilirubin ≤ 1.5×ULN, serum creatinine (SCr) ≤ 1.5×ULN, and serum albumin (ALB) ≥ 30 g/L;
• Patients with heart disease, echocardiogram showing that the left ventricular ejection fraction ≥ 50%, electrocardiogram (ECG) is basically normal within 4 weeks before operation and with no obvious symptoms are acceptable;
• There is no serious underlying disease that could lead to an expected life expectancy < 5 years;
• Willing to sign the informed consent for participation and publication of results.

Exclusion Criteria:

• Human epidermal growth factor receptor 2 (HER2)-positive or indeterminate G/GEJ cancer;
• Pregnant or lactating women;
• Positive pregnancy test for women in childbearing age. Menopausal women without menstruation for at least 12 months can be regarded as women with no possibility of getting pregnant;
• Refusal of birth control during the study;
• Prior chemotherapy, radiotherapy or immunotherapy;
• History of other malignant diseases in the last 5 years (except for cervical carcinoma in situ);
• History of uncontrolled central nervous system diseases, which could influence the compliance;
• History of severe liver diseases (Child-Pugh class C), renal diseases (endogenous creatinine clearance rate (Ccr) ≤ 50 ml/min or SCr > 1.5 ULN) or respiratory diseases; Uncontrolled diabetes and hypertension; Clinically severe heart disease, such as symptomatic coronary heart disease, New York Heart Association (NYHA) class II or more severe congestive heart failure, uncontrolled arrhythmia requiring drug intervention, or a history of myocardial infarction in the last 6 months;
• History of dysphagia, complete or partial gastrointestinal obstruction, active gastrointestinal bleeding and gastrointestinal perforation;
• On steroid treatment after organ transplant;
• With uncontrolled severe infections;
• Known dihydropyrimidine dehydrogenase deficiency (DPD);
• Anaphylaxis to any research drug ingredient;
• Known peripheral neuropathy (> NCI-CTC AE 1). Patients with only disappearance of deep tendon reflex need not to be excluded.