Conversion Therapy of Fruquintinib in Combination With Sintilimab and SOX in Unresectable Gastric Cancer

Inclusion Criteria:

• Signed the Informed Consent Form

• Ages: 18-75 Years (concluding 18 and 75 Years)

• Pathologically confirmed gastric/gastroesophageal junction adenocarcinoma, and meetsone of the following conditions: invasion of adjacent organs such as colon, tail ofpancreas and spleen; localized peritoneal metastasis; positive exfoliative cytologyof ascites; class I, class II, part of class III and very few class IV stage IVgastric adenocarcinoma according to biological behavior; N3; extensive or fusedlymph node metastasis; Krukenberg tumor; Liver metastasis limited to one lobe, lessthan 5cm in diameter, isolated abdominal aortic metastasis, etc;

• Untreated(e.g. radiotherapy, chemotherapy, target therapy and immunotherapy)

• Life expectancy greater than 3 months

• ECOG(Eastern Cooperative Oncology Group) :0~1

• Sufficient organ and bone marrow functions as follows:

1. Absolute Neutrophil Count (ANC) ≥1.5×109/L, White Blood Cell≥3.5×109/L;

2. Platelet Count of ≥100×109/L;

3. Hemoglobin≥90g/L;

4. Total Bilirubin (TBIL) ≤1.5 x ULN;

5. ALT and AST<2.5 x ULN, GPT≤1.5×ULN; If there is liver metastasis, then ALT andAST<5.0 x ULN, GPT≤3.0×ULN;

6. Serum Creatinine (SCr) ≤1.0×ULN;

7. Endogenous creatinine clearance rate > 60ml / min (Cockcroft Gault formula);

• No severe dysfunction of heart, lung and liver; No jaundice and gastrointestinalobstruction; No acute infection

• Not participating in other clinical trials 4 weeks before and during the treatment

Exclusion Criteria:

• Known HER-2 positive

• Distal metastasis to lung, brain, and bone

• Have received operation on the stomach

• A history of other malignancies within 5 years prior to inclusion, except forcervical carcinoma in situ, basal or squamous cell skin cancer

• Patients with any active autoimmune disease or a documented history of autoimmunedisease within 4 weeks prior to enrollment

• Previously received allogeneic bone marrow transplantation or organ transplantation

• Known hypersensitivity to any of the study drugs or excipients

• Hypertension that is not controlled by the drug, and is defined as: SBP ≥150 mmHgand/or DBP ≥90 mmHg

• International normalized ratio (INR) > 1.5 or partially activated prothrombin time (APTT) > 1.5 × ULN

• Poorly controlled diabetes before enrollment

• Clinically significant electrolyte abnormalities judged by researchers

• With any diseases or conditions that affected drug absorption, or the patient couldnot take drugs orally

• Patients with obvious evidence of bleeding tendency or medical history within 3months before enrollment, hemoptysis or thromboembolism within 12 months

• Cardiovascular diseases with significant clinical significance, including but notlimited to acute myocardial infarction, severe / unstable angina pectoris orcoronary artery bypass grafting within 6 months before enrollment; Congestive heartfailure, New York Heart Association (NYHA) grade > 2; ventricular arrhythmiarequiring drug treatment; LVEF (left ventricular ejection fraction) < 50%

• Active infection or serious infection that is not controlled by drug (≥CTCAE v5.0Grade 2）

• 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)

• Women who are pregnant or lactating

• Urinary protein ≥ ++, and the 24-hour urine protein quantification is greater than 1.0 g

• 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 of the investigationalproduct or may affect interpretation of study results

• Patients considered unsuitable for inclusion in this study by the investigator.