Inclusion Criteria:
1. Fully understands the study and voluntarily provides written informed consent (ICF).
2. Histologically confirmed gastric adenocarcinoma or gastroesophageal junction (GEJ) adenocarcinoma that is unresectable, advanced, or metastatic.
3. HER2-negative and proficient mismatch repair (pMMR).
4. Moderate or greater volume of ascites at baseline.
5. Peritoneal metastasis confirmed by ascites cytology or laparoscopy.
6. Aged 18 to 75 years, regardless of sex.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 7 days before the first dose of study treatment.
8. Life expectancy of at least 3 months.
9. Adequate organ function, as defined by the following criteria:
Hematologic function, without blood transfusion, granulocyte colony-stimulating factor (G-CSF), or pharmacologic correction within 14 days before screening:
1. Neutrophil count ≥1.5 × 10\^9/L;
2. Platelet count ≥75 × 10\^9/L;
3. Hemoglobin ≥90 g/L.
Biochemical function, without albumin infusion within 14 days before screening:
4. Serum creatinine ≤1.5 × the upper limit of normal (ULN), or creatinine clearance \>50 mL/min;
5. Total serum bilirubin ≤1.5 × ULN; for patients with Gilbert syndrome, total bilirubin ≤3 × ULN is permitted;
6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN; for patients with liver metastases, AST and ALT ≤5 × ULN.
Coagulation function:
7. International normalized ratio (INR) ≤2.3, or prothrombin time (PT) prolonged by ≤6 seconds above the normal control range;
8. Urine protein \<2+; if urine protein is ≥2+, a 24-hour urine protein test may be performed, and patients with 24-hour urinary protein \<1.0 g may be enrolled.
Cardiac function:
9. New York Heart Association (NYHA) functional class \<III;
10. Left ventricular ejection fraction ≥50%.
10. For patients with active hepatitis B virus (HBV) infection, HBV DNA must be \<500 IU/mL (or \<2,500 copies/mL if the study center reports HBV DNA only in copies/mL), and the patient must be willing to receive continuous antiviral therapy throughout the study. Patients with positive hepatitis C virus (HCV) RNA must receive antiviral therapy according to local standard treatment guidelines, with liver function abnormalities no greater than CTCAE Grade 1.
11. Women of childbearing potential must have a negative serum pregnancy test within 28 days before enrollment and agree to use effective contraception during study treatment and for 60 days after the last dose. Women of childbearing potential are defined as sexually mature women who: (1) have not undergone hysterectomy or bilateral oophorectomy, and (2) have not experienced natural amenorrhea for at least 24 consecutive months. Amenorrhea following cancer treatment does not exclude childbearing potential. Female partners of male participants who are of childbearing potential must also comply with the above contraceptive requirements.
12. Patients must have adequate nutritional status, defined as body mass index (BMI) ≥18 kg/m2, body weight ≥40 kg, and serum albumin ≥3.0 g/dL.
Exclusion Criteria:
1. HER2-positive tumor, defined as IHC 3+ or IHC 2+ with FISH positivity, or dMMR/MSI-H.
2. Previous systemic therapy for unresectable advanced or metastatic GC/GEJ adenocarcinoma. Prior neoadjuvant or adjuvant therapy is permitted provided that treatment was completed at least 6 months before randomization and there was no disease progression.
3. Previous immunotherapy, including immune checkpoint inhibitors such as anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibodies; immune checkpoint agonists targeting ICOS, CD40, CD137, GITR, OX40, or other targets; or immune cell therapy.
4. Previous intraperitoneal chemotherapy, including hyperthermic intraperitoneal chemotherapy (HIPEC), pressurized intraperitoneal aerosol chemotherapy (PIPAC), or other intraperitoneal chemotherapy.
5. Any other active malignancy within the previous 5 years or concurrently with GC/GEJ adenocarcinoma. Patients with cured localized malignancies, such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the prostate, cervical carcinoma in situ, or breast carcinoma in situ, may be eligible.
6. Uncontrolled or moderate or greater pleural effusion or pericardial effusion.
7. A bleeding event within 3 months before the first dose requiring blood transfusion, invasive intervention, or hospitalization, or current bleeding symptoms requiring intervention, such as hemoptysis, hematuria, or hematochezia.
8. Thrombotic or embolic events within 6 months before initiation of study treatment, including cerebrovascular events such as transient ischemic attack, cerebral hemorrhage, or cerebral infarction, or pulmonary embolism.
9. Major surgery within 4 weeks before initiation of study treatment, except diagnostic procedures, or anticipated need for major surgery during the study.
10. Inability to swallow tablets, malabsorption syndrome, complete intestinal obstruction, or other conditions that may interfere with gastrointestinal absorption.
11. Previous or current central nervous system metastases.
12. Active autoimmune disease or a history of autoimmune disease with potential for recurrence, including but not limited to autoimmune hepatitis, interstitial pneumonitis, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, or hypothyroidism. Patients with hypothyroidism controlled by hormone replacement therapy may be enrolled. Patients with dermatologic conditions not requiring systemic treatment, such as vitiligo, psoriasis, or alopecia; controlled type 1 diabetes treated with insulin; or childhood asthma that has completely resolved and requires no intervention in adulthood may be enrolled. Patients with asthma requiring medical intervention with bronchodilators are not eligible.
13. Use of immunosuppressive agents or systemic corticosteroids for immunosuppressive purposes within 14 days before initiation of study treatment, at a dose \>10 mg/day prednisone or equivalent.
14. Congenital or acquired immunodeficiency, including human immunodeficiency virus (HIV) infection.
15. Receipt of a live attenuated vaccine within 28 days before initiation of study treatment, or anticipated need for such vaccination during study treatment or within 60 days after the last dose.
16. Receipt of cytotoxic antitumor therapy within 2 weeks before the first dose; or biological therapy, such as monoclonal antibodies, immunotherapy such as interleukins, interferons, or thymosin, or other investigational drugs within 4 weeks before the first dose.
17. Uncontrolled concomitant disease, including severe hypertension, decompensated cirrhosis, nephrotic syndrome, angina pectoris, severe arrhythmia, interstitial lung disease, uncontrolled metabolic disorders, severe active peptic ulcer disease or gastritis, severe bleeding tendency, or coagulation disorders.
18. Toxicities from previous antitumor therapy that have not recovered to CTCAE Grade 0-1, except for:
1. Alopecia;
2. Pigmentation;
3. Peripheral neurotoxicity recovered to \<CTCAE Grade 2;
4. Late toxicity caused by radiotherapy that, in the investigator's judgment, is not expected to recover.
19. Active tuberculosis (TB) requiring antituberculosis treatment.
20. Active hepatitis B or hepatitis C, defined as HBsAg positivity with detectable HBV DNA, or HBcAb positivity.
21. Pregnant or breastfeeding women.
