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 biopsyhistopathological examination.
4. Imaging (CT/MRI) and diagnostic laparoscopy confirmed at the stage of cT3/4a Nx or T2N+, M0(AJCC 8th) before randomization.
5. confirmed by immunohistochemistry (IHC) staining or genetic and transcriptionalprofiling detection to meet one of the following conditions:
6. Combined positive score (CPS) of PD-L1 protein expression ≥5.
7. Epstein-Barr virus-positive (EBV(+)).
8. mismatch repair-deficient (dMMR).
9. Microsatellite instability-high (MSI-H)
10. The Eastern Cooperative Oncology Group Performance status (ECOG PS) 0-1
11. Expected survival period ≥ 12 weeks
12. The main organ function meets the following criteria within 7 days before treatment:
13. Hemoglobin (Hb) level ≥9.0 g/dl
14. Neutrophil count (ANC)≥1.5×l09/L
15. Platelet (PLT) ≥100×109/L
16. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level ≤2.5×ULN
17. Alkaline phosphatase(ALP)level ≤2.5×ULN
18. Serum creatinine (Cr) level ≤1.5×ULN and creatinine clearance ≥60 ml/min
19. Thyroid stimulating hormone (TSH) level ≤1×ULN (if abnormal, should requirenormal 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 therapyfor 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:
6. Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1) or CTLA-4 agent
7. Prior therapy with tyrosine kinase inhibitor within 2 weeks.
8. Patients who have participated in other clinical trials of anti-tumor drugswithin four weeks
9. Have vaccination with attenuated live vaccines within 4 weeks prior to initiationof the study treatment or plan to vaccinate during the study;
10. Concurrent medical condition requiring the use of cortisol (>10mg/day Prednisoneor equivalent dose) or other systematic immunosuppressive medications within 14days before the study treatment. Except: inhalation or topical corticosteroids.Doses > 10 mg/day prednisone or equivalent for replacement therapy
11. Patients have experienced or currently has other malignancies within 5 years.
12. Patients have an active or history of autoimmune disease that may recur or requireimmunosuppressive drugs within 2 weeks or less or during the study. Or have a historyof immunodeficiency, including HIV-positive or other acquired, congenitalimmunodeficiency disease, or a history of organ transplantation
13. Patients with other severe acute or chronic conditions that may increase the risk ofparticipation in the study and study treatment, or may interfere with interpretationof study results, and judged by the investigator as not suitable for participation inthis clinical trial.
14. Within 2 weeks or 2 weeks before randomization, patients have an active oruncontrollable infection that requires systemic antibiotic treatment
15. Diagnosed with interstitial pneumonia, non-infectious pneumonia, pulmonary fibrosis,acute lung disease;
16. Patients with active tuberculosis or receiving previous anti-tuberculosis therapywithin one year
17. Women who are pregnant, breast-feeding or planning to become pregnant during treatmentor within 6 months after treatment ends.
18. Patients have a history of psychotropic substance abuse and are unable to quit or havea mental disorder