This single-center, prospective, single-arm Phase II clinical trial is designed to evaluate the efficacy and safety of combining hepatic artery infusion chemotherapy (HAIC, for up to 4 cycles) with iparomlimab/tuvonralimab plus bevacizumab followed by stereotactic body radiotherapy (SBRT) in patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) who present with portal vein tumor thrombus (PVTT) or extrahepatic oligometastatic disease. The study aims to determine whether this combination strategy can prolong progression-free survival (PFS), while also improving overall survival (OS), objective response rate (ORR), disease control rate (DCR), and local control rate (LCR), as well as maintaining quality of life (QoL). In addition, the trial will systematically evaluate the safety profile and treatment-related toxicities associated with this regimen.
Male or female patients aged between 18 and 70 years.
Unresectable HCC, BCLC Stage C according to the BCLC strategy-2025 update, with staging established via biopsy pathology and/or clinical diagnosis.
Child-Pugh class A without clinically significant hepatic decompensation; Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Metastatic burden and SBRT eligibility
Histopathological exclusions
Mixed HCC subtypes: Fibrolamellar HCC or sarcomatoid HCC or cholangiocarcinoma components
Curative local therapy candidacy
Current candidacy for resection, liver transplant, or RFA
Single group
Anti-VEGF
DrugDrug: Bevacizumab (15 mg/kg, IV, every 3 weeks)
Immunotherapy
DrugIparomlimab/tuvonralimab (7.5 mg/kg, IV, every 3 weeks, administered sequentially after bevacizumab)
Local Therapy
RadiationStereotactic Body Radiotherapy (SBRT), total dose of 25-40 Gy in 5 fractions over 1-2 weeks, targeting intrahepatic tumors, portal vein tumor, and/or limited extrahepatic oligometastatic lesions
hepatic arterial infusion chemotherapy (HAIC)
Procedure/SurgeryOn Day 1 of each cycle, HAIC using the HAIC-FO regimen will be initiated via a hepatic arterial catheter or pump and completed over 2-3 days, as follows: oxaliplatin 130 mg/m², leucovorin 200 mg/m², fluorouracil 400 mg/m² as a bolus, followed by fluorouracil 2,400 mg/m² by continuous infusion over 46 h. HAIC may be administered every 3 weeks for up to four cycles.
Progression-free survival (PFS)
The time between enrollment and disease progression or death for patients in the intent-to-treat population, whichever occurred first; for those who did not progress at the time of withdrawal from the study or whose time to disease progression was not recorded, the date of the last visit was used as the endpoint date.
Overall Survival (OS)
Time from initiation of treatment to death from any cause.
objective response rate (ORR)
The proportion of patients whose tumor size decreases (partial response) or disappears (complete response) after radiation based on RECIST 1.1.
Disease Control Rate (DCR)
The proportion of patients whose tumor size decreases (partial response), disappears (complete response), or is stable after radiation based on RECIST 1.1.
Local control rate (LCR)
The proportion of treated lesions without in-field local progression within the irradiated/target volume at prespecified time points (e.g., 6 and 12 months) per RECIST 1.1
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