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

Inclusion criteria

• Patients who fully understand the study and voluntarily sign the informed consent form (ICF).
• Age ≥ 18 years and ≤ 80 years.
• Patients with histopathologically confirmed unresectable or metastatic gastric cancer, with positive PD-L1 expression (CPS ≥ 1).
• Radiologically confirmed disease progression after prior first-line standard therapy.
• At least one measurable target lesion according to RECIST 1.1 criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2.
• Life expectancy ≥ 3 months.
• 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).
• 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).
• 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

• Hypersensitivity to any study drug or its components.
• 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.).
• Cardiac function and diseases meeting any of the following:

• Long QT syndrome or QTc interval > 480 ms;
• Complete left bundle branch block, or second- or third-degree atrioventricular block;
• Severe uncontrolled arrhythmia requiring medication;
• New York Heart Association (NYHA) class ≥ III;
• Left ventricular ejection fraction (LVEF) < 50%;
• 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.
• 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.
• Human immunodeficiency virus (HIV) infection (HIV antibody positive).
• Radiologically confirmed intestinal obstruction.
• 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).
• Pregnant or lactating women, and patients of childbearing potential who are unwilling to use contraception.
• Patients with other concurrent malignancies requiring treatment.
• Patients judged by the investigator to be unsuitable for participation in this study.
• 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.
• Arterial embolism, severe bleeding (excluding surgery-related bleeding), or severe bleeding tendency within 6 months prior to the first dose.
• Symptomatic brain metastases, meningeal metastases, spinal cord tumor invasion, or spinal cord compression.
• Use of strong inhibitors or inducers of CYP3A4, CYP2C8, or UGT1A1 within 14 days prior to study drug treatment.
• Use of other investigational drugs within 1 month prior to the first dose.
• Pregnant or lactating women, and subjects of childbearing potential who refuse contraception.