Fruquintinib Plus SOX as Neoadjuvant Therapy for Locally Advanced Gastric Adenocarcinoma

Inclusion Criteria:

1. Ages: 18-75 Years（concluding 18 and 75 Years）;
2. Pathologically confirmed resectable or potentially resectable locally advancedgastric/gastroesophageal junction adenocarcinoma (cT3/4aN+M0) ;
3. Bone scan should be performed if bone metastasis is suspected. If peritonealmetastasis is suspected, abdominal examination should be performed to exclude distantmetastasis；
4. ECOG PS 0-1, there was no deterioration within 7 days;
5. BMI≥18；
6. Has life expectancy of greater than 12 months；
7. No prior antitumor therapy (e.g., radiotherapy, chemotherapy, targeted therapy,immunotherapy, etc.)；
8. Have measurable lesions (according to RECIST 1.1);
9. The main organ functions meet the following criteria: (without blood transfusion orany blood component or cell growth factor within 14 days prior to enrollment):
10. Absolute Neutrophil Count (ANC)≥1.5×109/L, White Blood Cell≥4.0×109/L；
11. Platelet Count of ≥100×109/L；
12. Hemoglobin≥90g/L；
13. Total Bilirubin (TBIL)≤1.5 x ULN；
14. ALT and AST≤2.5 x ULN；
15. Urea/Urea Nitrogen（BUN）and Creatinine（Cr）≤1.5×ULN (and creatinine clearance (CCr)≥ 50mL/min);
16. Left Ventricular Ejection Fraction (LVEF)≥50%;
17. Electrocardiogram (ECG) Corrected QT Interval (QTcF)<470ms;
18. INR≤1.5×ULN，APTT≤1.5×ULN;

Exclusion Criteria:

1. Received anti-VEGF/VEGFR-targeted drugs and progressed upon these drugs;
2. HER 2+;
3. Live vaccines were administered within 4 weeks prior to enrollment or possibly duringthe study period;
4. A history of other malignancies within 5 years prior to inclusion, except for cervicalcarcinoma in situ, basal or squamous cell skin cancer, localized prostate cancertreated with radical surgery, and ductal carcinoma in situ treated with radicalsurgery;
5. Patients with any active autoimmune disease or a documented history of autoimmunedisease within 4 weeks prior to enrollment;
6. Previously received allogeneic stem cell or parenchymal organ transplantation;
7. Previously with serious cardiovascular disease, including unstable angina ormyocardial infarction within 6 months prior to enrollment;
8. Known hypersensitivity to any of the study drugs or excipients;
9. Distant metastasis to any part of the body；
10. Have received other investigational treatments in clinical studies within 4 weeksprior to enrollment;
11. Any significant clinical or laboratory abnormality that the investigator considers toinfluence the safety evaluators;
12. Hypertension that is not controlled by the drug, and is defined as: SBP ≥150 mmHgand/or DBP ≥90 mmHg；
13. With any diseases or conditions prior to enrollment that affected drug absorption, orpatients could not take drugs orally;
14. Have a gastrointestinal disease or condition that investigators suspect may affectdrug absorption, including, but not limited to, active gastric and duodenal ulcers,ulcerative colitis and other digestive disease, gastrointestinal tumor with activebleeding, or other gastrointestinal conditions that may cause bleeding or perforation,according to the investigator's judgement;
15. History or presence of a serious hemorrhage (>30 ml within 3 months), hemoptysis (>5ml blood within 4 weeks) or life threatening thromboembolic event within 12 months;
16. Have clinically significant cardiovascular disease, including but not limited to,acute myocardial infarction; severe/unstable angina pectoris or coronary artery bypassgrafting within 6 months prior to enrollment; congestive heart failure according tothe New York Heart Association (NYHA) classification ≥ 2; ventricular 26 arrhythmiaswhich needs drug treatment; or left ventricular ejection fraction (LVEF) <50%;
17. Active infection or serious infection that is not controlled by drug (≥CTCAE v5.0Grade 2）;
18. History of clinically significant hepatic disease, including, but not limited to,known hepatitis B virus (HBV) infection with HBV DNA positive (copies ≥1×104/ml);known hepatitis C virus infection with HCV RNA positive (copies ≥1×103/m); or livercirrhosis, etc;
19. Adverse events (AEs) due to previous anti-tumor therapy has not recovered to CommonTerminology Criteria for Adverse Event (CTCAE) ≤Grade 1. Alopecia, lymphocytopenia,and grade 2 neurotoxicity due to oxaliplatin are not included;
20. Women who are pregnant or lactating;
21. With blood transfusion or any blood component or cell growth factor within 14 daysprior to enrollment;
22. Have any other disease, metabolic disorder, physical examination anomaly, abnormallaboratory result, or any other conditions which, according to judgement of theinvestigator, renders the patient inappropriate for using the investigational productor affect interpretation of study results;
23. Urine routine indicates urinary protein ≥ ++, and the 24-hour urine proteinquantification is greater than 1.0 g;
24. Patients considered unsuitable for inclusion in this study by the investigator.