Toripalimab Combined With Chemotherapy as Neoadjuvant Treatment of Gastric Cancer

1. Pathologically confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma, siwert type I was excluded.
2. Clinical determined T3/4 N any or T 1/2 N 2/3 referred to AJCC 8, based on CT, gastroscopy, endoscopic ultrasound, gastrointestinal angiography, general ultrasound, or laparoscope if the patient can afford.
3. No prior chemotherapy and/or immunotherapy and/or radiation therapy.
4. Age 18 to 75 years old.
5. ECOG 0 or 1 .
6. Adequate Organ Function Laboratory Values Hb≥90g/L, WBC≥3.5×109 /L, ANC≥1.5×109 /L, Platelets≥100×109 /L Serum creatinine ≤1.0×ULN ALT≤1.5 ×UNL , AST ≤1.5×ULN，ALP≤ 1.5 ×ULN Serum total bilirubin ≤1.5 × ULN
7. Signed Informed consent

Exclusion Criteria:

1. Pathology types other than adenocarcinoma, such as squamous cell carcinoma.
2. intra-abdominal dissemination or distant metastasis (M1).
3. Digestive tract obstruction or repeated bleeding which can not be controlled, clinically significant ascites.
4. Those who cannot swallow pills.
5. Cirrhosis caused by any cause.
6. Heart function NYHA > I degree
7. Previous myocardial infarction, unstable angina, stroke and uncontrolled arrhythmia.
8. with any contraindications for surgery.
9. Previously received chemotherapy and or radiation therapy.
10. Previously received any anti-PD 1 , anti - PD L1/L2 antibodies, anti-CTLA 4 antibodies and other immunotherapy.
11. Previously received other anti-tumor treatments.
12. History of surgical resection for gastric cancer.
13. Have had other tumors in the past, except for cured skin cancer and cervical cancer in situ.
14. Accompanied by systemic diseases which cannot meet the conditions of chemotherapy.
15. Pregnancy and lactating patients.
16. History of mental diseases.
17. Poor compliance.
18. Active central nervous system (CNS) metastases and/or carcinomatous meningitis.
19. History of gastrointestinal perforation and/or fistula in the past 6 months; history of intestinal obstruction (including incomplete intestinal obstruction which need for extraintestinal Nutritional); inflammatory bowel disease or extensive bowel resection(Partial colon resection or extensive small Intestinal resection complicated with chronic diarrhea);Crohn's disease; ulcerative colitis or chronic diarrhea.
20. History of interstitial pneumonia, drug-induced pneumonia, idiopathic pneumonia or active pneumonia.
21. Active tuberculosis (TB), undergoing anti-tuberculosis treatment or within 1 year before the first dose
22. has infected Human immunodeficiency virus (HIV1 / 2 antibody positive).
23. Has known active hepatitis B or hepatitis C. Acute or chronic active hepatitis B or hepatitis C virus infection, hepatitis B virus (HBV) DNA > 2000 IU / ml or 10\^4 copies / ml; Hepatitis C virus (HCV) RNA > 10\^3 copies / ml ; hepatitis B surface antigen(HbsAg) and anti-HCV antibody is positive at the same time.
24. Severe infections active or poorly controlled. Severe infections within 4 weeks before the first dose, includes but not limited to hospitalization attributed to infection, bacteremia or severe pneumonia complications.
25. Active autoimmune disease requiring systemic treatment or the history within 2 years (one with vitiligo, psoriasis, alopecia or Graves' disease not requiring systemic treatment in the last 2 years, hypothyroidism only requiring thyroid hormones alternative treatment and type 1 diabetes only requiring insulin replacement therapy can be enrolled). Have has known history of primary immunodeficiency. patients with positive autoimmune antibodies only will need to be confirmed the presence of autoimmune diseases according to the investigator's judgment.
26. Application of immunosuppressive drugs within the latest 4 weeks, excluding nasal glucocorticoids and topical glucocorticoids by inhaling or other routings. Physiological doses of systemic glucocorticoids (prednisone not exceeding 10 mg/day or equivalent dose of other glucocorticoids) and temporary use of glucocorticoids for the treatment of dyspnea caused by asthma, chronic obstructive pulmonary disease and other diseases would be allowed.
27. have received live attenuated vaccines within 4 weeks or intend to be vaccinated during the study period.
28. have received systemic immunostimulant treatment within 4 weeks.
29. Have undergone major surgery (such as craniotomy, thoracotomy or laparotomy) within 4 weeks, or unhealed wound, ulcer or fracture at present.
30. Have uncontrolled metabolic disorders , other non-malignant tumors, systemic diseases or secondary reactions originated from the cancer which may lead to higher medical risks and/or the uncertainty of survival evaluation.
31. patients with other acute or chronic diseases, psychiatric disorders, or abnormal laboratory tests that may lead to the increasing risk of participating the research and drug administration, or interference results Interpretation, whom may be excluded from the study according to the investigator's judgment.