Perioperative chemotherapy improves overall survival (OS) and disease-free survival (DFS) compared with surgery alone in patients with resectable gastric adenocarcinoma (GA) or gastro-oesophageal junction adenocarcinoma (GEJA). The addition of tislelizumab and trastuzumab to chemotherapy improves outcomes in patients with HER2-positive advanced gastric cancer (GC), and the investigators aimed to explore its role in the perioperative setting.

This study will evaluate the pathologic complete response rate of a perioperative chemotherapy combined with tislelizumab and Trastuzumab in patients with resectable gastric cancer. Prior to surgery to resect the tumor, tislelizumab (intravenously, 200 mg on day 1 of every cycle) and trastuzumab (intravenously, 8 mg/kg loading dose, then 6 mg/kg on days 1 of every cycle) will be administered for four cycles and the perioperative chemotherapy contains docetaxel (intravenously, 50 mg/m2 on day 1 of every cycle) and S1 (orally, 400mg/m2 BID on day 1~14 of every cycle) and Oxaliplatin(intravenously, 100 mg /m2 on day 1 of every cycle) will be administered for three cycles prior to surgery.If complete resection, R0 or microscopic residual tumor R1 is achieved, patients will continue with three cycles of SOX and tislelizumab and trastuzumab and then for completion of 12 months treatment with tislelizumab and trastuzumab alone.

Key Inclusion Criteria:

• provide archive tumor tissue samples or accept fresh tumor tissue biopsy(Sample requirements are: formalin-fixed and paraffin-embedded wax blocks of tumor tissue or at least 20 unstained tumor specimen slides).

• assessed by the surgery can be removed, histology/confirmed HER2 positive cytology and the integration of a stomach esophagus carcinoma.

  • CT2-4CN any C M0 or T any CN +M0, AJCC/UICC TNM staging of gastric cancer (8th edition).
  • The HER2 receptor protein status was assessed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) using the following methods.Tumors with an IHC 3+ score are considered HER2-positive.Patients with immunohistochemical 2+ tumors were given FISH tests to determine FISH positive samples.
  • Abdominal computed tomography (CT), abdominal, pelvic, and/or echo-endoscopy were performed 2 weeks before surgery to assess resectability.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 or 2.

• have no received no any anti-tumor treatment, including surgery, chemotherapy, targeted therapy, immune therapy.

• Adequate organ function (No blood transfusion or hematopoietic stimulating factor therapy was received within 14 days. Absolute neutrophil count (ANC) ≥1.5×109/L Platelet count ≥75×109/L Hemoglobin ≥80 g/L. Serum total bilirubin ≤1.5×ULN. total bilirubin must be <3×ULN) Prothrombin time/international normalized ratio (PT/INR) ≤1.5×ULN and activated partial thromboplastin time (aPTT) ≤1.5×ULN.Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤3×ULN. For subjects with liver metastases, AST and ALT must be ≤5×ULN for subjects with liver metastases. Creatinine clearance rate (Ccr) ≥50ml/min（according to the Cockcroft-Gault formula）. Urine protein qualitative≤1+ ;Or urinary protein qualitative ≥2+, 24 hours urinary protein < 1g)

Key Exclusion Criteria:

• A history of any other malignancy in the past 5 years (except carcinoma in situ or basal cell carcinoma of the skin or squamous cell carcinoma of the skin)
• Received other unmarketed investigational drug or therapy within 4 weeks prior to initial investigational drug use.
• A major organ surgery (excluding needle biopsy) or significant trauma occurred within 4 weeks prior to initial investigational drug use.
• Requires systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration to treat a current condition.

Exceptions include: topical, ocular, intraarticular, intranasal, and inhaled glucocorticoids;Short-term use of glucocorticoids for preventive treatment (e.g. to prevent contrast allergy)

• Use of immunoregulatory drugs, including but not limited to thymosin, interleukin-2, interferon, etc., within 14 days prior to initial use of the study drug.
• Has been administered a live vaccine within 4 weeks prior to Cycle1 Day 1.
• Previous recipient of allogeneic hematopoietic stem cell transplantation or organ transplantation.
• Previous adverse reactions to other medications have not recovered to CTCAE 5.0 level ≤1 (Other toxicities, such as hair loss, were not considered to pose a safety risk).
• Symptomatic peripheral neuropathy was evaluated as > 2 with CTCAE 5.0.
• Has central nervous system metastases or meningeal metastases.
• Inability to swallow medications orally, or other gastrointestinal diseases (such as total intestinal obstruction, etc.) that may affect the absorption of oral medications.
• Patients who had an active infection within 1 week prior to the first use of the study drug and who currently require systemic anti-infective therapy.
• has a history of alcohol or drug abuse or dependence.
• Known history of Human Immunodeficiency Virus (HIV).
• Untreated chronic hepatitis B viral (HBV) infection or chronic HBV carrier with HBV DNA ≥200 IU/mL (or 1000 copies/mL),prophylaxis antiviral therapy other than interferon is allowed ,or active hepatitis C virus (HCV) should be excluded.
• Current patients with interstitial lung disease.
• Has a history of severe cardiovascular and cerebrovascular disease, including but not limited to: has serious heart rhythm or abnormal conduction;Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events occurred within 6 months prior to D1 ;New York heart association (NYHA), cardiac function class II or higher and left ventricular ejection fraction (LVEF) < 50%; clinical uncontrol of high blood pressure.
• Patients with active, or previous and recurrent autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.) were excluded from patients with clinically stable autoimmune thyroid disease.
• Grade 3 or higher arteriovenous thromboembolism events or bleeding events occurred within 6 months prior to the first use of the study drug;Or present with grade ≥2 bleeding or factors determined by the investigator to have a higher blood risk (such as active gastrointestinal ulcer or esophageal varicose veins or tumor invasion of major blood vessels).
• Gastrointestinal perforation, abdominal fistula or intraperitoneal abscess occurred within 6 months prior to the first use of the study drug;Or a risk factor for cavity perforation/fistula formation (e.g., tumor infiltration of the outer wall of the cavity wall) currently identified by the investigator.
• Patients who allergies to the study drugs.
• People with mental disorders or poor compliance.
• Women who are pregnant or lactating.
• The investigator considers the subject to have a history of other serious systemic disease or for other reasons unsuitable for participation in this clinical study.