A Phase II Study of Irinotecan Liposome Plus Fruquintinib and Sintilimab in Second-Line PD-L1-Positive Advanced Gastric Cancer

Inclusion Criteria:

1. Patients who fully understand the study and voluntarily sign the informed consent form (ICF).
2. Age ≥ 18 years and ≤ 80 years.
3. Patients with histopathologically confirmed unresectable or metastatic gastric cancer, with positive PD-L1 expression (CPS ≥ 1).
4. Radiologically confirmed disease progression after prior first-line standard therapy.
5. At least one measurable target lesion according to RECIST 1.1 criteria.
6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2.
7. Life expectancy ≥ 3 months.
8. Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L, platelet count ≥ 100 × 10\^9/L, and hemoglobin ≥ 90 g/L (with no blood transfusion, no blood products, and no use of granulocyte colony-stimulating factor or other hematopoietic growth factors for correction within 14 days prior to laboratory testing).
9. Hepatic and renal function: serum creatinine ≤ 1.5 × the upper limit of normal (ULN); AST and ALT ≤ 2.5 × ULN (≤ 5 × ULN for patients with liver metastases); total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN for patients with liver metastases).
10. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to enrollment, and must be willing to use appropriate contraception during the study and for 6 months after the last dose of study drug.

Exclusion Criteria:

1. Hypersensitivity to any study drug or its components.
2. Concurrent severe uncontrolled infection or other severe uncontrolled concomitant diseases, or moderate or severe renal impairment (e.g., progressive infection, uncontrolled hypertension, diabetes mellitus, etc.).
3. Cardiac function and diseases meeting any of the following:

   1. Long QT syndrome or QTc interval \> 480 ms;
   2. Complete left bundle branch block, or second- or third-degree atrioventricular block;
   3. Severe uncontrolled arrhythmia requiring medication;
   4. New York Heart Association (NYHA) class ≥ III;
   5. Left ventricular ejection fraction (LVEF) \< 50%;
   6. Myocardial infarction, unstable angina, history of severe unstable ventricular arrhythmia or any other arrhythmia requiring treatment, history of clinically significant pericardial disease within 6 months prior to enrollment, or ECG evidence of acute ischemia or active conduction system abnormality.
4. Active hepatitis B or hepatitis C infection (hepatitis B surface antigen positive and hepatitis B virus DNA \> 1 × 10\^3 copies/mL; hepatitis C virus RNA \> 1 × 10\^3 copies/mL); asymptomatic chronic hepatitis B or hepatitis C carriers may be exempted.
5. Human immunodeficiency virus (HIV) infection (HIV antibody positive).
6. Radiologically confirmed intestinal obstruction.
7. History of or concurrent other malignancies (except adequately controlled non-melanoma basal cell carcinoma of the skin, carcinoma in situ of the breast/cervix, and other malignancies that have been effectively controlled without treatment within the past five years).
8. Pregnant or lactating women, and patients of childbearing potential who are unwilling to use contraception.
9. Patients with other concurrent malignancies requiring treatment.
10. Patients judged by the investigator to be unsuitable for participation in this study.
11. History of pulmonary hemorrhage/hemoptysis ≥ grade 2 (defined as at least 2.5 mL of bright red blood) within 1 month prior to the first dose.
12. Arterial embolism, severe bleeding (excluding surgery-related bleeding), or severe bleeding tendency within 6 months prior to the first dose.
13. Symptomatic brain metastases, meningeal metastases, spinal cord tumor invasion, or spinal cord compression.
14. Use of strong inhibitors or inducers of CYP3A4, CYP2C8, or UGT1A1 within 14 days prior to study drug treatment.
15. Use of other investigational drugs within 1 month prior to the first dose.
16. Pregnant or lactating women, and subjects of childbearing potential who refuse contraception.