CAPOX Plus Sintilimab and Bevacizumab Biosimilar (IBI305) for Neoadjuvant Treatment of Locally Advanced Gastric Cancer

Inclusion Criteria:

1. Age 18-75 years.
2. Histologically or cytologically confirmed diagnosis of locally advanced G/GEJ adenocarcinoma (cT3N+/T4aNany M0) as assessed by exploratory laparoscopic surgery, ultrasonography and/or CT/MRI.
3. Resectable G/GEJ cancer, as judged by experienced surgeons.
4. There was no previous antitumor treatment.
5. The expected survival is more than 3 months.
6. ECOG PS≤1.
7. Adequate organ function including the following:

   1. Total bilirubin ≤1.5 times the upper limit of normal (ULN);
   2. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤3×ULN;
   3. Alkaline phosphatase≤2.5×ULN (if the tumor invaded the liver, ≤3×ULN);
   4. Serum creatinine≤1.5×ULN;
   5. Serum amylase and lipase≤1.5×ULN;
   6. International standardized ratio (INR)/partial thromboplastin time (PTT)≤1.5×ULN;
   7. Platelet count ≥ 100,000 /mm3;
   8. Hemoglobin (Hb) ≥ 9 g/dL;
   9. Absolute neutrophil count (ANC) ≥ 1500/mm3;
8. Strict contraception.
9. Patients must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure.

Exclusion Criteria:

1. Undergoing other drug clinical trials or having participated in any drug clinical trials one month before enrollment.
2. Active autoimmune disease or history of refractory autoimmune disease.
3. Receiving corticosteroids (\> 10mg/d prednisone or equivalent dose of steroids) or other systematic immunosuppression therapies within 14 days before enrollment, excluding the following therapies: steroid hormone replacement therapy (≤10mg/d); local steroid therapy; and short-term, prophylactic steroid therapy for preventing allergies or nausea and vomiting.
4. Active or clinically significant cardiac disease:

   1. Congestive heart failure \> New York Heart Association (NYHA) class 2;
   2. Active coronary artery disease;
   3. Arrhythmias requiring treatment other than β-blockers or digoxin;
   4. Unstable angina (with angina symptoms at rest), new angina within 3 months before enrollment, or new myocardial infarction within 6 months before enrollment
5. Evidence or history of bleeding diathesis or coagulopathy.
6. Grade 3 bleeding events 4 weeks before enrollment.
7. Thromboembolism or arteriovenous events, such as cerebrovascular events (including transient ischemic attack), deep vein thrombosis or pulmonary embolism, occurred 6 months before enrollment.
8. Currently taking anticoagulants.
9. Gastrointestinal perforation, gastrointestinal obstruction, or uncontrollable diarrhea 6 months before enrollment.
10. Other tumors that have not been treated or exist at the same time, except carcinoma in situ of the cervix, treated basal cell carcinoma or superficial bladder tumor. If the tumor was cured and no evidence of disease was found for more than 3 years, the patient can be enrolled. All other tumors must be treated at least 3 years before enrollment.
11. Patients with pheochromocytoma.
12. Patients with a history of HIV infection or active hepatitis B/C.
13. Ongoing \> level 2 infection.
14. Symptomatic brain metastasis or meningioma.
15. Unhealed wounds, ulcers or fractures.
16. Renal failure patients requiring blood or peritoneal dialysis.
17. Epileptic that needs medication.
18. Active, symptomatic interstitial pneumonia, pleural or ascites that causes dyspnea (dyspnea ≥ 2 grade).
19. History of organ transplantation (including corneal transplantation).
20. Allergic to research drugs or similar drugs, or suspected allergies.
21. Pregnant or lactating women.
22. Medical, psychological or social conditions can affect the recruitment of patients and evaluation of study results.
23. Other antitumor therapy (chemotherapy, radiotherapy, surgery, immunotherapy, biotherapy, chemoembolization) other than investigator drugs. Palliative external irradiation for non-target lesions is allowed.
24. Previously used oxaliplatin, capecitabine, ICIs and anti-angiogenesis drugs;
25. Major surgery 4 weeks before recruitment, open biopsy or major trauma surgery (excluding biliary stents, or percutaneous biliary drainage).
26. Treatment with antitumor Chinese herbal medicine.
27. History of allogeneic blood transfusion within 6 months.
28. Vaccination history within 4 weeks before enrollment.
29. The investigator believes that patients who are not suitable for the study.