Fruquintinib Combined With Toripalimab and SOX Regimen in the First-line Treatment of Advanced Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

Inclusion Criteria:

* Pathologically determined unresectable advanced gastric or gastroesophageal junction adenocarcinoma;
* 18-75 years old (including 18 and 75 years old);
* No previous anti-tumor treatment for metastatic diseases;
* HER2 negative;
* Eastern Cooperation Oncology Group (ECOG) performance status of 0-1;
* Life expectancy ≥ 3 months;
* At least one measurable lesion according to RECIST version 1.1;
* Adequate organ and bone marrow functions:

Absolute neutrophil count≥1.5x10\^9/L; Platelet count≥100x10\^9/L; Hemoglobin≥9g/dL; Serum bilirubin≤1.5x the upper limit of normal(ULN); Alanine aminotransferase(ALT) and aspartate aminotransferase(AST)≤1.5x ULN; Serum creatinine≤1.5x ULN; Endogenous creatinine clearance rate ≥ 50ml / min;

* Women of childbearing age need to take effective contraceptive measures.

Exclusion Criteria:

* Previous treatment with vascular endothelial growth factor receptor (VEGFR) inhibitors or previous use of immune checkpoint inhibitors;
* Other malignant tumors in the past 5 years, except for skin basal cell or squamous cell carcinoma after radical surgery, or cervical carcinoma in situ;
* There was central nervous system (CNS) metastasis or previous brain metastasis before enrollment;
* Patients with autoimmune diseases or history of autoimmune diseases within 4 weeks before enrollment;
* Previously received allogeneic bone marrow transplantation or organ transplantation;
* Uncontrolled malignant ascites;
* Participated in other unapproved or unlisted drug clinical trials in China within 4 weeks before enrollment, and received corresponding experimental drug treatment;
* Cardiovascular disease, including unstable angina or myocardial infarction, occurred within 6 months before the start of study treatment;
* Subjects allergic to the study drug or any of its adjuvants;
* International normalized ratio (INR) \> 1.5 or partially activated prothrombin time (APTT) \> 1.5 × ULN；
* The researchers judged clinically significant electrolyte abnormalities;
* At present, the patient has hypertension that cannot be controlled by drugs, which is specified as: systolic blood pressure ≥ 140 mmHg and / or diastolic blood pressure ≥ 90 mmHg;
* Patients currently have poorly controlled diabetes (fasting glucose level is greater than CTCAE grade 2 after regular treatment);
* Patients with dysphagia, active peptic ulcer, intestinal obstruction, active gastrointestinal bleeding, peptic perforation, malabsorption syndrome or uncontrolled intestinal inflammatory diseases;
* Any disease or state affecting drug absorption before enrollment, or the patient cannot take oral medication;
* Patients with obvious evidence of bleeding tendency or medical history within 3 months before enrollment, hemoptysis or thromboembolism within 12 months;
* Cardiovascular diseases with significant clinical significance, including but not limited to acute myocardial infarction, severe / unstable angina pectoris or coronary artery bypass grafting within 6 months before enrollment;
* Ventricular arrhythmia requiring drug treatment;
* Congestive heart failure ≤New York Heart Association (NYHA) class 2;
* LVEF \< 50%;
* Active or uncontrolled severe infection ≥ grade 2 according to National Cancer Institute Common Toxicity (NCI-CTC) criteria;
* With positive urine protein and 24-hour urinary protein content\>1g;
* Known human immunodeficiency virus (HIV) infection; known history of clinically significant liver disease, including viral hepatitis;
* Pregnant (positive pregnancy test before medication) or lactating women;
* Complications require long-term immunosuppressive treatment, or systemic or local use of immunosuppressive corticosteroids (\> 10mg / day prednisone or other therapeutic hormones);
* By judgment of the investigator, there are concomitant diseases that seriously endanger the safety of the patient or affect the completion of the study.