Inclusion Criteria:
1. Have fully understood the study and voluntarily signed the informed consent;
2. Aged 18-75 years (including 18 and 75 years);
3. Pathologically confirmed or potentially resectable locally advanced gastric/gastroesophageal junction adenocarcinoma (cT2-T4b, N+M0);
4. If bone metastasis is suspected, a bone scan should be performed. If peritoneal metastasis is suspected, abdominal examination should be performed to rule out distant metastasis.
5. At least 1 measurable lesion according to RECIST v1.1 criteria;
6. United States Eastern Cancer Consortium (ECOG) Physical status score 0-1; BMI≥18;
7. Expected survival ≥12 weeks;
8. The functions of vital organs during the first 14 days of enrollment met the following requirements:
* Absolute neutrophil count ≥1.5×109/L;
* Platelet ≥80×109/L;
* Hemoglobin ≥90g/L;
* Total bilirubin \< 1.5 ULN; ALT and AST \< 2.5 ULN (\< 5 ULN in patients with liver metastasis);
* Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance (CCr)≥60ml/min;
* endogenous creatinine clearance \> 50ml/min;
9. Female subjects of childbearing age or male subjects whose sexual partner is a female of childbearing age should take effective contraceptive measures during the whole treatment period and 6 months after the treatment period;
10. Good compliance, cooperate with follow-up.
Exclusion Criteria:
1. Known HER2-positive patients;
2. Participated in other drug clinical trials and received at least one drug therapy within 4 weeks prior to enrollment or received other systemic anti-tumor therapy, including chemotherapy, signal transduction inhibitors, immunotherapy, and other investigational drugs within 4 weeks prior to enrollment;
3. Had other malignancies within 5 years prior to admission, except basal cell or squamous cell carcinoma of the skin after radical surgery, or carcinoma in situ of the cervix;
4. Receive live vaccine within 4 weeks prior to enrollment or possibly during the study period;
5. Had active autoimmune disease or history of autoimmune disease within 4 weeks prior to enrollment;
6. Previously received allogeneic bone marrow transplantation or organ transplantation;
7. The patient has a current disease or condition that affects drug absorption, or the patient cannot take Fruquintinib orally;
8. Subjects who are allergic to the investigational drug or any of its adjuncts;
9. The investigator identified clinically significant electrolyte abnormalities;
10. Hypertension that could not be controlled by drugs before enrollment was defined as: systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg;
11. Gastrointestinal diseases such as active ulcer of stomach and duodenum, ulcerative colitis, or active bleeding of unresectable tumors, or other conditions that may cause gastrointestinal bleeding or perforation as determined by researchers before enrollment;
12. Patients with significant evidence or history of bleeding tendency within 3 months (bleeding \>30 mL within 3 months, accompanied by hematemesis, stool, and blood in the stool), hemoptysis (\>5 mL of fresh blood within 4 weeks), or thromboembolic events (including stroke events and/or transient ischemic attacks) within 12 months prior to admission;
13. History of severe cardiovascular and cerebrovascular diseases:
* Cerebrovascular accident (excluding lacunar infarction, minor cerebral ischemia, or transient ischemic attack), myocardial infarction, unstable angina, and poorly controlled arrhythmias (including QTc interval ≥ 450ms for men and 470 ms for women) within 6 months prior to first administration of the study drug (QTc interval Fridericia) Formula calculation);
* New York Heart Association (NYHA) heart function Grade \> II or left ventricular ejection fraction (LVEF) \< 50%;
14. Known human immunodeficiency virus (HIV) infection; A known history of clinically significant liver disease, including viral hepatitis \[active HBV infection, i.e., positive HBV DNA (\>1×104 copies /mL or \>2000 IU/ml) must be excluded for a known hepatitis B virus (HBV) carrier; Known hepatitis C virus infection (HCV) and HCV RNA positive (\>1×103 copies /mL), or other hepatitis, cirrhosis\];
16\. Women who are pregnant (positive pregnancy test before medication) or breastfeeding; 17. Two consecutive routine urine tests indicated urine protein ≥2+, and the urine protein volume \>1.0g within 24 hours of reexamination; 18. Patients with ascites or pleural effusion with clinical symptoms; 19. CTCAE V5.0 grade 1 or higher toxicity due to any previous anticancer treatment that is not resolved, excluding oxaliplatin induced alopecia, lymphocytopenia, and neurotoxicity ≤ grade 2; 20.Patients considered inappropriate for inclusion in this study.
