Combination treatment for advanced gastric and gastro-esophageal junction cancer

Inclusion Criteria:

1. Patients voluntarily participate in this study and sign informed consent forms;
2. 18-75 years old;
3. Patients whose tumor has been pathologically diagnosed as gastric adenocarcinoma or gastroesophageal junction adenocarcinoma, and has not received any type of antitumor treatment (such as surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.);
4. Confirmed TNM staging by CT or MRI as resectable cT3-4N+M0;
5. ECOG score is 0-1;
6. Patients who are able to swallow pills and capsules normally;
7. Patients whose expected survival period is longer than 12 weeks;
8. The function of important organs meets the following requirements:

A. Absolute number of neutrophils (ANC) ≥1.5×10\^9/L B. Platelet number ≥90×10\^9/L; C. Hemoglobin ≥90g/L; D.Total bilirubin ≤1.5×ULN; ALT, AST and/or AKP≤2.5×ULN; E. Serum creatinine ≤1.5×ULN or creatinine clearance rate \>60mL/min (Cockcroft-Gault); F. Activated partial thromboplastin time (APTT) and international standardization ratio (INR) ≤1.5×ULN (for anticoagulation treatments using stable doses such as low-molecular heparin or warfarin and INR can be screened within the expected treatment range of anticoagulants); 9. Female patients with fertility must undergo a blood pregnancy test within 72 hours before the first administration of the drug and the result is negative. During the study period and at least 6 months after the last dose of the study drug, a medically approved contraceptive measure (such as intrauterine birth control device, contraceptive pill or condom) must be used; for men, it should be surgery, sterilization, or agree to use effective contraception during the study period and within 6 months after the last dose of the study drug.

Exclusion Criteria:

1. Patients who are known to have peritoneal metastasis or positive peritoneal lavage cytology (CY1P0) or have distant metastasis;
2. Patients whose tumor can not be resected by surgery for tumor reasons or comorbidity or patients who refuse to undergo surgery;
3. Patients who have other malignant tumors within the past 5 years or at the same time, except for cured skin basal cell carcinoma, cervical in situ and breast cancer in situ;
4. The toxicity of previous anti-tumor treatment has not recovered to CTCAE≤grade one (NCI CTCAEv5.0), except for hair loss (any level allowed) and peripheral neuropathy (need to be ≤grade two );
5. Active bleeding;
6. Patients who had gastrointestinal perforation, abdominal abscess or recent intestinal obstruction or imaging and clinical symptoms with intestinal obstruction in the past 3 months;
7. Uncontrollable hypertension, symptomatic cardiac insufficiency, and severe heart disease within 6 months, including but not limited to:

(1) Acute coronary syndrome; (2) Arrhythmias that require drug treatment or have clinical significance, or do not interrupt the use of drugs that may lead to QT prolongation during the research period; (3) Acute myocardial infarction; (4) Heart failure; (5) Any other heart disease judged by the researchers to be unsuitable for participating in this trial.

8\. Patients who have active ulcers, unhealed wounds or fractures; 9. Patients who need antimicrobial treatment in the stage of active infection; 10. Active hepatitis (Hepatitis B reference: HBsAg positive and HBV DNA ≥500IU/ml; hepatitis C reference: HCV antibody positive and HCV virus copy number \> normal value upper limit); 11. Patients with congenital or acquired immunodeficiency; 12. Patients who are planning to receive or have previously received organ or allogeneic bone marrow transplantation; 13. At present, patients who are accompanied by interstitial pneumonia or interstitial lung disease, or who have a previous history of interstitial pneumonia or interstitial lung disease that require hormone treatment, or other patients who may interfere with the judgment and treatment of immune-related pulmonary toxicity, fibrosis, organic pneumonia (such as occlusion bronchiolitis), pneumoconiosis, drug-related pneumonia, idiopathic pneumonia, or screening CT showing active pneumonia or severe pulmonary function impairment; active pulmonary tuberculosis; 14. Patients with any active autoimmune diseases or a history of autoimmune diseases with the possibility of recurrence \[including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism (patients who can only be controlled by hormone replacement therapy can be included in the group)\]; patients with skin diseases that do not require systemic treatment, such as leukoplakia, psoriasis, hair loss, patients with type I diabetes that can be controlled by insulin treatment or have a history of asthma, but who have been completely relieved in childhood and do not require any intervention can be included in the group; asthma patients who need the intervention of bronchodilators cannot be included in the group; 15. Patients who are using immunosuppressive drugs or systemic corticosteroid treatment within 7 days before joining in the group to achieve the purpose of immunosuppression (\>10mg/day of prednisone or other equivalent drugs); 16. Patients who have received live attenuated vaccine within 28 days before joining in the group, or need to inject such vaccines during treatment or within 60 days after the last dose; 17. Oral or intravenous antibiotics or intravenously within 4 weeks before joining the group (except for preventive antibiotics administered intravenously for no more than 48 hours); 18. Known allergies to any study drugs or excipients; 19. Participated in clinical research of other drugs 4 weeks before joining in the group; 20. Lactating women; 21. According to the researcher's judgment, the patient has other factors that may affect the research results or cause the forced termination of this study, such as alcoholism, drug abuse, other serious diseases (including mental illness that need combined treatment, and serious laboratory examination abnormalities, accompanied by family or social factors, which will affect the safety of patients);