Neoadjuvant Immunotherapy and Chemotherapy for Locally Advanced Esophagogastric Junction and Gastric Cancer Trial

Inclusion Criteria:

1. Written (signed) informed consent;
2. Age ≥ 18 years and ≤75 years.
3. Confirmed gastric and gastroesophageal junction adenocarcinoma by Gastroscopic biopsy histopathological examination.
4. Imaging (CT/MRI) and diagnostic laparoscopy confirmed at the stage of cT3/4a Nx or T2 N+, M0(AJCC 8th) before randomization.
5. confirmed by immunohistochemistry (IHC) staining or genetic and transcriptional profiling detection to meet one of the following conditions:

   1. Combined positive score (CPS) of PD-L1 protein expression ≥5.
   2. Epstein-Barr virus-positive (EBV(+)).
   3. mismatch repair-deficient (dMMR).
   4. Microsatellite instability-high (MSI-H)
6. The Eastern Cooperative Oncology Group Performance status (ECOG PS) 0-1
7. Expected survival period ≥ 12 weeks
8. The main organ function meets the following criteria within 7 days before treatment:

   1. Hemoglobin (Hb) level ≥9.0 g/dl
   2. Neutrophil count (ANC)≥1.5×l09/L
   3. Platelet (PLT) ≥100×109/L
   4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level ≤2.5×ULN
   5. Alkaline phosphatase(ALP)level ≤2.5×ULN
   6. Serum creatinine (Cr) level ≤1.5×ULN and creatinine clearance ≥60 ml/min
   7. Thyroid stimulating hormone (TSH) level ≤1×ULN (if abnormal, should require normal serum free thyroid hormone (T4) and Normal serum free triiodothyronine (T3))

Exclusion Criteria:

1. Confirmed at stage IV (AJCC 8th) or unresectable by investigator before randomization.
2. Prior chemotherapy, radiotherapy, surgery immunotherapy or molecular targeted therapy for gastric cancer;
3. Patients who have HER2 positive confiemed with IHC3+ or IHC2+ and FISH positive
4. Patients are allergic to study medication and its ingredients
5. Patients with a history of following treatments:

   1. Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1) or CTLA-4 agent
   2. Prior therapy with tyrosine kinase inhibitor within 2 weeks.
   3. Patients who have participated in other clinical trials of anti-tumor drugs within four weeks
   4. Have vaccination with attenuated live vaccines within 4 weeks prior to initiation of the study treatment or plan to vaccinate during the study;
   5. Concurrent medical condition requiring the use of cortisol (\>10mg/day Prednisone or equivalent dose) or other systematic immunosuppressive medications within 14 days before the study treatment. Except: inhalation or topical corticosteroids. Doses \> 10 mg/day prednisone or equivalent for replacement therapy
6. Patients have experienced or currently has other malignancies within 5 years.
7. Patients have an active or history of autoimmune disease that may recur or require immunosuppressive drugs within 2 weeks or less or during the study. Or have a history of immunodeficiency, including HIV-positive or other acquired, congenital immunodeficiency disease, or a history of organ transplantation
8. Patients with other severe acute or chronic conditions that may increase the risk of participation in the study and study treatment, or may interfere with interpretation of study results, and judged by the investigator as not suitable for participation in this clinical trial.
9. Within 2 weeks or 2 weeks before randomization, patients have an active or uncontrollable infection that requires systemic antibiotic treatment
10. Diagnosed with interstitial pneumonia, non-infectious pneumonia, pulmonary fibrosis, acute lung disease;
11. Patients with active tuberculosis or receiving previous anti-tuberculosis therapy within one year
12. Women who are pregnant, breast-feeding or planning to become pregnant during treatment or within 6 months after treatment ends.
13. Patients have a history of psychotropic substance abuse and are unable to quit or have a mental disorder