Clinical Study of Envafolimab Combined With Fruquintinib and Chemotherapy for Neoadjuvant Treatment of Gastric Cancer

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 advancedgastric/gastroesophageal junction adenocarcinoma (cT2-T4b, N+M0);

4. If bone metastasis is suspected, a bone scan should be performed. If peritonealmetastasis is suspected, abdominal examination should be performed to rule outdistant 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 thefollowing 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 patientswith 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 afemale of childbearing age should take effective contraceptive measures during thewhole 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 therapywithin 4 weeks prior to enrollment or received other systemic anti-tumor therapy,including chemotherapy, signal transduction inhibitors, immunotherapy, and otherinvestigational drugs within 4 weeks prior to enrollment;

3. Had other malignancies within 5 years prior to admission, except basal cell orsquamous cell carcinoma of the skin after radical surgery, or carcinoma in situ ofthe cervix;

4. Receive live vaccine within 4 weeks prior to enrollment or possibly during the studyperiod;

5. Had active autoimmune disease or history of autoimmune disease within 4 weeks priorto 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 thepatient 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, ulcerativecolitis, or active bleeding of unresectable tumors, or other conditions that maycause gastrointestinal bleeding or perforation as determined by researchers beforeenrollment;

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 inthe stool), hemoptysis (>5 mL of fresh blood within 4 weeks), or thromboembolicevents (including stroke events and/or transient ischemic attacks) within 12 monthsprior to admission;

13. History of severe cardiovascular and cerebrovascular diseases:

• Cerebrovascular accident (excluding lacunar infarction, minor cerebralischemia, or transient ischemic attack), myocardial infarction, unstableangina, and poorly controlled arrhythmias (including QTc interval ≥ 450ms formen and 470 ms for women) within 6 months prior to first administration of thestudy drug (QTc interval Fridericia) Formula calculation);

• New York Heart Association (NYHA) heart function Grade > II or leftventricular ejection fraction (LVEF) < 50%;

14. Known human immunodeficiency virus (HIV) infection; A known history of clinicallysignificant 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 aknown hepatitis B virus (HBV) carrier; Known hepatitis C virus infection (HCV) andHCV RNA positive (>1×103 copies /mL), or other hepatitis, cirrhosis];

15. Women who are pregnant (positive pregnancy test before medication) or breastfeeding;

16. Two consecutive routine urine tests indicated urine protein ≥2+, and the urineprotein volume >1.0g within 24 hours of reexamination; 18. Patients with ascitesor pleural effusion with clinical symptoms; 19. CTCAE V5.0 grade 1 or highertoxicity due to any previous anticancer treatment that is not resolved, excludingoxaliplatin induced alopecia, lymphocytopenia, and neurotoxicity ≤ grade 2; 20.Patients considered inappropriate for inclusion in this study.