Fruquintinib in Combination With Sintilimab and CAPEOX as First-line Treatment for G/GEJ Cancer

Inclusion Criteria:

1. Subjects aged 18-75 years (including 18 and 75 years);
2. Understand the research procedure and content, and voluntarily sign a written informedconsent;
3. Incurable advanced/recurrent gastric or gastroesophageal junction adenocarcinoma withhistopathological and/or cytological confirmation of HER2-negative or HER2 statusunknown;
4. There is at least one measurable lesion according to RECIST 1.1 criteria;
5. No previous treatment with VEGFR-targeting drugs or PD-1/PD-L1 monoclonal antibody.Patients who had received platinum or paclitaxel or fluorouracil adjuvant chemotherapyafter surgery and recurred more than 6 months after the end of chemotherapy withoutgrade 2 toxicity or higher could be enrolled.
6. Physical condition score (ECOG PS score) : 0-1 score;
7. Expected survival ≥3 months;
8. The main organs function well;That is, the relevant check indicators within 14 daysbefore randomization meet the following requirements: Hemoglobin ≥ 90 g/L (no transfusion within 14 days); Neutrophil count > 1.5×109/L;Platelet count ≥ 100×109/L; Total bilirubin ≤ 1.5×ULN (upper limit of normal); Serumglutamic pyruvic aminotransferase (ALT) or serum glutamic oxalacetic aminotransferase (AST) ≤ 2.5×ULN; If there is liver metastasis, ALT or AST ≤ 5×ULN; Endogenouscreatinine clearance ≥ 60 ml/min (Cockcroft-Gault formula); Cardiac Doppler ultrasoundassessment: left ventricular ejection fraction (LVEF) ≥ 50%; Thyroid function index:thyroid stimulating hormone (TSH), free thyroxine (FT3/FT4) in the normal range;
9. Weight of more than 40 kg (including 40 kg), or BMI > 18.5
10. Women who are fertile must have a negative urine or serum pregnancy test within 7 daysprior to randomization and must consent to use highly effective contraception duringthe study period and for at least 120 days after the last administration offruquintinib and sintilimab and for at least 180 days after the last administration ofchemotherapy (Appendix 9);
11. Men who are not sterilized must consent to use highly effective contraception duringthe study period and for at least 120 days after the last administration offruquintinib and sintilimab and for at least 180 days after the last administration ofchemotherapy (Appendix 9).

Exclusion Criteria:

1. Patients with other malignant tumors in the past or at the same time, but have beencured of early tumors, including skin basal cell carcinoma, cervical carcinoma insitu, stage I lung cancer, stage I colorectal cancer and other tumors that researchersjudge will not affect the patient's life in the short term can be excluded;
2. Participated in other drug clinical trials within four weeks;
3. have multiple factors that affect oral medication (such as inability to swallow,chronic diarrhea, and intestinal obstruction);
4. Have a history of bleeding, any bleeding event with a severity rating of CTCAE5.0 orhigher occurring within 4 weeks prior to screening;
5. Patients with known central nervous system metastasis or history of central nervoussystem metastasis before screening. For patients with clinically suspected CNSmetastasis, CT or MRI examination must be performed within 28 days before enrollmentto rule out CNS metastasis.
6. Patients with hypertension who are not well controlled by single antihypertensivemedication (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90mmHg);Patients with history of unstable angina pectoris; Patients with newly diagnosedangina pectoris or myocardial infarction within 3 months prior to screening;Arrhythmias (including QTcF: ≥450 ms in men and ≥470 ms in women) requiring long-termuse of antiarrhythmic drugs and New York Heart Association grade ≥II cardiacinsufficiency;
7. long-term unhealed wounds or incomplete healing fractures;
8. Imaging shows that the tumor has invaded important blood vessels, or the investigatordetermines that the patient's tumor is highly likely to invade important blood vesselsduring treatment and cause fatal massive bleeding;
9. Patients with abnormal coagulation function and bleeding tendency (14 days beforerandomization must meet: INR in the normal range without the use of anticoagulants, orno clinically significant abnormalities); Patients treated with anticoagulants orvitamin K antagonists such as warfarin, heparin, or their analogs; Low doses ofwarfarin (1 mg orally, once daily) or low doses of aspirin (up to 100 mg daily) arepermitted for prophylactic purposes if INR ≤ 1.5;
10. Occurrence of arteriovenous thrombosis events within 6 months prior to screening, suchas cerebrovascular accident (including temporary ischemic attack), deep veinthrombosis (except venous thrombosis caused by intravenous catheterization in previouschemotherapy and cured by investigators), pulmonary embolism, etc.;
11. Urine routine indicated urinary protein ≥++ and confirmed 24-hour urinary proteinquantity > 1.0g;
12. Have used immunotargeted therapy drugs;
13. Have a history of immunodeficiency, or other acquired or congenital immunodeficiencydiseases, or have a history of organ transplantation;
14. Patients with infectious pneumonia, non-infectious pneumonia, interstitial pneumoniaand other patients requiring corticosteroids;
15. A history of serious chronic autoimmune diseases, such as systemic lupuserythematosus; History of ulcerative enteritis, Crohn's disease and other inflammatorybowel diseases, irritable bowel syndrome and other chronic diarrheal diseases; Ahistory of sarcoidosis or tuberculosis; History of active hepatitis B, hepatitis C andHIV infection; Well controlled non-severe immune diseases such as dermatitis,arthritis, psoriasis, etc. can be included. Hepatitis B virus drops <1000copy/ml couldbe included in the group.
16. Patients with hypersensitivity to human or murine monoclonal antibodies;
17. Those who have a history of psychotropic drug abuse and cannot quit or have mentaldisorders;
18. pleural effusion or abdominal effusion with clinical symptoms requiring clinicalintervention;
19. Patients who do not follow medical advice, do not use drugs according to regulations,or have incomplete data that can affect the evaluation of efficacy or safety;
20. In the judgment of the investigator, there is a serious concomitant disease thatendangers the patient's safety or interferes with the patient's completion of thestudy.