FOLFOX-HAIC Combined With Donafenib and Pucotenlimab as First-Line Treatment for Unresectable Intrahepatic Cholangiocarcinoma

Prior treatment

• Previous treatment with anti-PD-1/PD-L1 antibodies, anti-CTLA-4 antibodies, or other immunomodulatory agents.
• History of gastrointestinal bleeding, esophageal or gastric varices with bleeding risk, or other active bleeding within 6 months prior to enrollment.

Other illness

• Known hypersensitivity or allergy to Oxaliplatin, Fluorouracil, Leucovorin, Donafenib, Pucotenlimab, or any of their excipients.
• Diagnosis of other malignant tumors within the past 5 years (excluding cured basal cell carcinoma of the skin or carcinoma in situ of the cervix).
• Active, known, or suspected autoimmune disease (e.g., systemic lupus erythematosus, rheumatoid arthritis) requiring systemic treatment.
• Severe cardiovascular disease, including unstable angina, myocardial infarction within 6 months, or uncontrolled hypertension.
• Active infection requiring systemic antibiotic therapy.
• Hepatitis B virus (HBV) DNA \> 2000 IU/mL (participants must receive antiviral treatment to suppress viral load).
• Known Human Immunodeficiency Virus (HIV) infection or active Syphilis infection.
• Any condition that, in the opinion of the investigator, would jeopardize the safety of the participant or the integrity of the study data.

Other

• Presence of central nervous system (CNS) metastases.
• Anatomy unsuitable for hepatic arterial catheterization (e.g., severe vascular variation or occlusion).
• Pregnant or breastfeeding women.

• Male or female participants aged 18 to 75 years.
• Histologically or clinically diagnosed Hepatocellular Carcinoma (HCC) according to AASLD or EASL guidelines.
• Disease stage classified as Barcelona Clinic Liver Cancer (BCLC) stage B (unresectable) or stage C.
• No prior systemic treatment for advanced HCC (treatment-naïve).
• At least one measurable lesion according to RECIST v1.1 criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Child-Pugh liver function class A (score 5-6).
• Life expectancy of at least 3 months.
• Adequate bone marrow function: Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L, Platelets ≥ 75 × 10\^9/L, and Hemoglobin ≥ 90 g/L.
• Adequate liver function: Total bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 5 × ULN.
• Adequate renal function: Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min.
• Adequate coagulation function: INR ≤ 1.5 or PT ≤ 1.5 × ULN.
• Participants suitable for hepatic artery catheterization and HAIC treatment as assessed by the investigator.
• Willingness to provide written informed consent.