A Study of Liposomal Irinotecan Plus 5-FU/LV HAIC With Lenvatinib and a PD-1 Inhibitor in Advanced ICC

Prior treatment

• Significant clinical bleeding symptoms or tendency within 3 months prior to treatment (e.g., \>30 mL bleeding, hematemesis, melena, hematochezia), hemoptysis (\>5 mL of fresh blood within 4 weeks). Venous/thrombotic events within the past 6 months (e.g., cerebrovascular accident, deep vein thrombosis, pulmonary embolism). Requirement for long-term anticoagulation (e.g., warfarin, heparin) or antiplatelet therapy (Aspirin ≥300 mg/day or Clopidogrel ≥75 mg/day).
• Use of strong CYP3A4 inducers within 3 weeks prior to first dose, or use of strong CYP3A4 inhibitors or strong UGT1A1 inhibitors within 3 weeks prior to first dose.
• Major organ surgery within 4 weeks prior to treatment (excluding needle biopsy, central venous catheter placement, port implantation, biliary stenting, percutaneous transhepatic biliary drainage, cholecystostomy) or planned elective surgery.
• Congenital or acquired immunodeficiency (e.g., HIV infection), or active hepatitis (abnormal liver enzymes; for Hepatitis B: HBV DNA ≥1000 IU/mL; for Hepatitis C: HCV RNA ≥1000 IU/mL). Chronic HBV carriers with HBV DNA \<2000 IU/ml can be enrolled if they receive concurrent antiviral therapy during the trial.

Other illness

• History of other malignancies within the past 5 years (except cured carcinoma in situ or basal cell skin cancer).
• Bowel obstruction (except incomplete obstruction manageable with enteral nutrition) or patients at risk of bowel perforation (e.g., acute diverticulitis, abdominal abscess, history of abdominal cancer).

Lab values

• Active cardiac disease within 6 months prior to treatment, including myocardial infarction, severe/unstable angina. Left ventricular ejection fraction (LVEF) \<50% by echocardiogram, or poorly controlled arrhythmia.
• Any other disease, metabolic disorder, physical examination finding, or laboratory abnormality that, in the investigator's judgment, contraindicates the use of the study drug, may affect result interpretation, or places the patient at high risk.

Other

• Extensive distant metastasis (e.g., peritoneal metastasis, multiple bone/brain metastases).
• Pregnant or lactating female participants.

• Aged 18 to 75 years.
• Histologically or cytologically confirmed unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma (ICC).
• Liver function: Child-Pugh class A (score 5-6) or good class B (score ≤7).
• At least one measurable lesion as defined by RECIST 1.1 criteria.
• ECOG performance status of 0 or 1.
• Life expectancy greater than 12 months.
• No prior systemic therapy for unresectable locally advanced or metastatic ICC. Prior adjuvant or neoadjuvant chemotherapy is allowed if completed \>6 months before recurrence.
• Adequate bone marrow function: Absolute Neutrophil Count (ANC) ≥1.5×10⁹/L, Hemoglobin ≥90 g/L, Platelet count (PLT) ≥100×10⁹/L, White Blood Cell count (WBC) ≥3.0×10⁹/L.
• Adequate renal function: Serum creatinine (Cr) ≤1.5 × ULN or Creatinine Clearance (CCr) ≥60 mL/min (calculated by Cockcroft-Gault formula).
• Adequate coagulation function: Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), and International Normalized Ratio (INR) ≤1.5 × ULN.
• No active or suspected infection.
• Not pregnant or lactating. Female and male participants of childbearing potential must use effective contraception during the study and for 6 months after the last dose.
• Good compliance, ability to understand the study procedures, and provision of signed informed consent.