Overview

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.

Eligibility

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.