Sintilimab in Combination With S-1/Oxaliplatin With Nab-paclitaxel Intraperitoneal Infusion for Untreated Advanced Gastric Cancer With Malignant Ascites

Inclusion Criteria:

1. Have fully understood the research and voluntarily signed the informed consent;
2. Gastric adenocarcinoma or gastroesophageal junction adenocarcinoma confirmed bypathology, and unresectable advanced or metastatic disease;
3. HER2 negative, mismatch repair-proficient (pMMR);
4. Moderate or above volume of ascites at baseline;
5. Peritoneal metastasis confirmed by ascites cytology or laparoscopy;
6. Aged from 18 to 75 years old, regardless of gender;
7. Within 7 days before the first administration of the study drug, the ECOG score is 0-2;
8. Expected survival period ≥ 3 months;
9. Adequate organ function: Routine Blood Test: (no blood transfusion, no use of granulocyte colony-stimulatingfactor [G-CSF], no drug correction within 14 days prior to screening):
10. Neutrophils ≥ 1.5×109/L;
11. Platelets ≥ 75×109/L;
12. Hemoglobin ≥ 90g/L; Biochemical examination: (No albumin infusion within 14 days before screening):
13. Serum creatinine ≤ 1.5 × upper limit of normal ULN, or creatinine clearance > 50mL/min;
14. Serum total bilirubin ≤ 1.5×ULN (patients with Gilbert syndrome are allowed tohave total bilirubin ≤ 3×ULN);
15. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5×ULN; forpatients with liver metastasis, ALT and AST ≤ 5×ULN; Coagulation:
16. International normalized ratio (INR) ≤ 2.3 or prothrombin time (PT) exceeding thenormal control range ≤ 6 seconds;
17. Urinary protein < 2+ (if urinary protein ≥ 2+, 24-hour (h) urine proteinquantification can be performed, and 24-h urine protein quantification < 1.0 gcan be included in the study) Cardiac Function:
18. New York Heart Association (NYHA) classification <3;
19. Left ventricular ejection fraction ≥ 50%;
20. Within 28 days before enrollment, women of childbearing age must confirm that theserum pregnancy test is negative and agree to use effective contraception during theuse of the study drug and within 60 days after the last dose.
21. Patients must have an appropriate nutritional status: BMI ≥ 18 kg/m2, body weight ≥ 40kg, and serum albumin ≥ 28 g/L.

Exclusion Criteria:

1. HER2-positive (IHC3+ or IHC2+ and FISH-positive at the same time) or dMMR/MSI-H;
2. Previously received systemic therapy for advanced unresectable or metastatic GC/GEJadenocarcinoma. Patients can previously receive neoadjuvant therapy or adjuvanttherapy, as long as it ends at least 6 months before this diagnosis without progress;
3. Previously received immune checkpoint inhibitors (such as anti-PD-1 antibody,anti-PD-L1 antibody, anti-CTLA-4 antibody, etc.), immune checkpoint agonists, immunecell therapy and other immunotherapy.
4. Previously received intraperitoneal chemotherapy, including hyperthermicintraperitoneal chemotherapy (HIPEC), pressurized intraperitoneal aerosol chemotherapy (PIPAC), intraperitoneal chemotherapy, etc.
5. Other active malignant tumors other than GC/GEJ adenocarcinoma within 5 years or atthe same time. Localized tumors that have been cured can be enrolled, such as basalcell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladdercancer, carcinoma in situ of the prostate, carcinoma in situ of the cervix, carcinomain situ of the breast, etc.;
6. Uncontrolled or moderate and above pleural effusion, pericardial effusion;
7. Hemorrhagic events that require blood transfusion, invasive intervention orhospitalization occurred within 3 months before the first administration, or currentlyhave bleeding symptoms and require intervention (such as hemoptysis, hematuria, bloodystool);
8. Thrombosis or embolism events occurred within 6 months before the start of studytreatment, such as cerebrovascular accidents (including transient ischemic attack,cerebral hemorrhage, cerebral infarction), pulmonary embolism, etc.;
9. Received major surgical treatment (except for diagnosis) within 4 weeks before thestart of study treatment or expected major surgical treatment during the study period;
10. Inability to swallow tablets, malabsorption syndrome, complete intestinal obstructionand other conditions affecting gastrointestinal absorption;
11. There have been or are currently central nervous system metastases;
12. Active autoimmune disease or history of autoimmune disease and possible relapse;
13. Using immunosuppressant or systemic hormone therapy within 14 days before starting thestudy treatment to achieve the purpose of immunosuppression;
14. Patients with congenital or acquired immune deficiency (such as HIV infection);
15. Received attenuated live vaccine treatment within 28 days before starting the studytreatment, or need to receive such vaccine during the expected treatment or within 60days after the last dose;
16. Received anti-tumor cytotoxic drug therapy within 2 weeks before the firstadministration; or received biological drug therapy, immunotherapy within 4 weeksbefore the first administration; or other study drug therapy;
17. There are currently uncontrolled comorbidities, such as severe hypertension,decompensated cirrhosis, nephrotic syndrome, angina pectoris, severe arrhythmia,interstitial lung disease, uncontrolled metabolic disorders, severe active pepticulcer disease or gastritis, severe bleeding tendency or coagulation disorder;
18. The toxicity of previous anti-tumor therapy has not recovered to CTCAE 0-1 grade;
19. Suffering from active tuberculosis (TB) and receiving anti-tuberculosis treatment;
20. Patients with active hepatitis B or C (positive HBsAg and positive HBV DNA copynumber; positive HBcAb);
21. Pregnant or lactating women.