Neoadjuvant Serplulimab in Combination With Chemotherapy in Locally Advanced Gastric or Gastro-esophageal Junction Cancer

Inclusion Criteria:

• histologically documented adenocarcinoma of Gastric or Gastroesophageal Junction. 2.clinically diagnosed stage T3-4aN+M0 according to ultrasound endoscopy or enhancedCT/MRI scan. 3. Male or female. Age ≥ 18 years and ≤75 years. 4. surgeonsparticipating in this study consider the lesion a resectable one. 5. ECOG 0~1 6.Physical condition and adequate organ function to ensure the success of abdominalsurgery. 7. Adequate hematological function: Neutrophil count ≥ 1.5 × 109/L,Platelets ≥ 100 × 109/L and Hemoglobin ≥90g/L. 8. Adequate liver function: Totalbilirubin ≤ 1.5 × upper limit of normal (ULN); AST (SGOT) and ALT (SGPT) < 2.5 × ULN . ALP ≤ 2.5 × upper limit of normal (ULN); ALB ≥30g/L. 9. Adequate renal function:Serum creatinine ≤ 1.5 x ULN, and creatinine clearance ≥ 60 ml/min. 10. Adequatecoagulation function: INR/PT≤ 1.5 x ULN, aPTT≤ 1.5 x ULN. 11. No serious concomitantdisease that will threaten the survival of patients to less than 5 years. 12.Written (signed) informed consent. 13. Good compliance with the study procedures,including lab and auxiliary examination and treatment. 14. Female patients shouldnot be pregnant or breast feeding. 15. PD-L1 assessment

Exclusion Criteria:

• patients with distant metastasis or unresectable primary lesion. 2. patients withT1, T2 lesion according to CT/MRI or ultrasound endoscopy. 3. history of chemo,radiation, immune therapy or radical resection for the GC/GEJ. 4. patients withactive autoimmune disease or history of refractory autoimmune disease. 5. patientswith active malignant tumor in recent 2 years, except the tumor studied in thisresearch or cured locally tumor like resected basal cell or squamous cell skincancer, superficial bladder cancer, cervical or breast carcinoma in situ. 6.uncontrollable pleural effusion, pericardial effusion, or ascites in 2 weeks beforerecruitment. 7. patients who have digestive tract bleeding in 2 weeks beforerecruitment or with high risk of bleeding. 8. perforation / fistula of GI tract in 6months before recruitment. 9. patients with upper GI tract obstruction or functionalabnormality or malabsorption syndrome, which can affect absorption of S-1. 10.losing over 20% body weight in 2 months before recruitment. 11. pulmonary diseasehistory: interstitial pulmonary disease, non-infective pneumonitis, pulmonaryfibrosis, acute pulmonary disease. 12. uncontrollable systemic diseases, includingdiabetes, hypertension, etc. 13. severe chronic or active infections in need ofsystemic antibacterial, antifungal, or antiviral treatment, including TB or HIV,etc. 14. patients with untreated chronic hepatitis B or HBV DNA over 500 IU/ml orpositive HCV RNA. 15. patients with any cardiovascular risk factors below:

1. cardiac chest pain occurring in 28 days before recruitment, defined as moderatepain that limits daily activity.

2. pulmonary embolism with symptoms occurring in 28 days before recruitment.

3. acute myocardial infarction occurring in 6 months before recruitment.

4. any history of heart failure reaching grade 3/4 of NYHA in 6 months beforerecruitment.

5. ventricular arrhythmias of Grade 2 or grater in 6 months before recruitment, oraccompanied by supraventricular tachyarrhythmias requiring medical treatment.

6. cerebrovascular accident within 6 months before recruitment. 16. patients withperipheral neuropathy NCI CTC AE grade 1, except those with only deep tendonreflex disappearing. 17. moderate or severe renal injury [creatinine clearancerate≤50 ml/min (according to Cockroft & Gault equation)], or Scr>1.5 x ULN. 18.dipyrimidine dehydrogenase (DPD) deficiency. 19. allergic to any drug in thisstudy. 20. history of allogeneic stem cell transplantation or organtransplantation. 21. use of steroids (dosage>10mg/d prednisone) or othersystemic immune suppressive therapy in 14 days before recruitment, exceptpatients treated with regimens below: a. steroids for hormone replacement (dosage>10mg/d prednisone); b. steroids for local application with littlesystemic absorption; c. short -term (≤ 7 days) steroids for preventing allergyor vomiting. 22. vaccinated with live vaccine in 4 weeks before recruitment.

7. receiving immune (interleukin, interferon, thymin) treatment or treatmentof other trials in 28 days before recruitment. 24. receiving palliativeradiation in 14 days before recruitment. 25. history of anti PD-1, PD-L1, PD-L2or any other specific T cell costimulation or checkpoint pathway targetedtreatment. 26. receiving operation in 28 days before recruitment, only if theoperation is a minimally invasive one e.g. PICC. 27. for patients withuncontrolled epilepsy, CNS diseases or history of mental disorder, researchersshould evaluate whether their diseases will impede their signing of informedconsent or compliance of treatment.