Clinical Study of Camrelizumab, Apatinib Mesylate and Nab-paclitaxel Combined With Oxplatin and S-1 in the Neoadjuvant Treatment of Locally Advanced Gastric Cancer With Different Genotypes

Inclusion criteria

• Age from 18 to 75 years, all sex；
• Primary gastric adenocarcinoma (papillary, tubular, mucinous, signet ring cell, or poorly differentiated) confirmed pathologically by histology or cytology；
• CT/MRI,PET-CT or laparoscopic exploration were used to confirm the diagnosis of gastric cancer staging as cT2-4a and/or N+ and M0 before operation.；
• measurable lesions at least should be detected by CT/MRI examination in accordance with the RECIST1.1.（CT scan of tumor lesion length≥10mm，CT scan short diameter of lymph node≥15mm，scan slice thickness 5mm）;
• ECOG（Eastern Cooperative Oncology Group）PS（Performance Status）:0-1 scores;
• the expected survival time is more than 12 weeks;
• the main organ function is normal, which should meet the following criteria: （1）(1)blood routine examination standards should be met（no blood transfusion within 14 days）

• HB≥100g/L，
• WBC≥3×109/L
• ANC≥1.5×109/L，
• PLT≥100×109/L； （2）biochemical examination shall comply with the following criteria：

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• BIL <1.5normal upper limit（ULN），
• ALT和AST<2.5ULN，GPT≤1.5×ULN；
• serum Cr≤1ULN，creatinine clearance rate>60ml/min（Cockcroft-Gault formula）
• women of childbearing age must have a pregnancy test in 7 days before entering the group (in serum), and the results were negative, and willing to use appropriate contraception during the study period and the last 8 weeks after giving drug; men should have the surgical sterilization, or adopt the appropriate contraceptive methods during the test and the last 8 weeks after giving drug.；
• No other clinical studies were conducted before and during the treatment； participants is willing to participate in this study, sign the informed consent, have good compliance, cooperate with follow-up.

Exclusion criteria

• Previous history of chemotherapy, radiotherapy, targeted drug therapy or immunotherapy
• Patients with contraindications for surgical treatment and chemotherapy or whose physical condition and organ function do not allow for major abdominal surgery；
• patients with metastasis；
• Having any active autoimmune diseases or a history of autoimmune diseases (such as interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); Patients with vitiligo or cured childhood asthma/allergies who did not need any intervention in adulthood were excluded; Autoimmune hypothyroidism treated with a stable dose of thyroid replacement hormone; Type 1 diabetes with stable doses of insulin；
• A history of immunodeficiency, including HIV testing positive, or other acquired or congenital immunodeficiency disorders, or a history of organ transplantation and allogeneic bone marrow transplantation；
• Accompanied by serious heart, lung, liver, kidney disease; Have nerve, mental disease; Jaundice or obstruction of the digestive tract with severe infection；
• pregnant or lactating women；
• The blood pressure of patients with hypertension cannot be reduced to the normal range by the antihypertensive drugs (systolic pressure >140 mmHg, diastolic pressure >90 mmHg)；
• With Ⅰ magnitude of coronary heart disease, arrhythmia (including QTc protracted between male > 450 ms, women > 470 ms) and cardiac insufficiency；
• Patients have a clear tendency with gastrointestinal bleeding, including the following situation: local active ulcerative lesions, and fecal occult blood (+ +); with melena and hematemesis history in 2 months; and patients with fecal occult blood (+) and coagulation dysfunction (INR(international normalized ratio)>1.5, APTT(activated partial thromboplastin time)>1.5 ULN), with bleeding tendency;；
• Subjects have failed to control good cardiovascular clinical symptoms or disease, including but not limited to: such as: (1) the NYHA class II heart failure or above (2) unstable angina pectoris (3) MI occurred within 1 year (4) have clinical significance of supraventricular or ventricular arrhythmias without clinical intervention on or after clinical intervention is still poorly controlled；
• History of interstitial lung disease (except radiation pneumonia without hormone therapy), and history of non-infectious pneumonia；
• Patients are positive of urine protein (urine protein detection 2+ or above, or 24 hours urine protein quantitative >1.0g)；
• A person who has previously been allergic to any component of the drug in this study； The researchers consider those who were not suitable for inclusion.