The purpose of this study is to learn how well a combination of iparomlimab and tuvonralimab (QL1706), lenvatinib, radiotherapy, and hepatic arterial infusion chemotherapy (HAIC) works and how safe it is for people with hepatocellular carcinoma (HCC) that has grown into the portal vein, forming a portal vein tumor thrombus (PVTT).
Participants will receive iparomlimab and tuvonralimab together with lenvatinib, radiotherapy directed at the portal vein tumor thrombus, and HAIC, which delivers chemotherapy directly through the hepatic artery. Researchers will evaluate how long the cancer remains controlled without getting worse, how much the tumors shrink, how long participants survive, and whether the treatment makes surgery possible for some participants. Treatment-related side effects will also be assessed.
The study will also explore whether features in tumor tissue and blood are associated with treatment response and may help identify patients who are more likely to benefit from this treatment strategy.
Age ≥18 and ≤75 years at the time of signing informed consent.
Histologically or clinically confirmed hepatocellular carcinoma (HCC) according to the 2024 Chinese Guidelines for the Diagnosis and Treatment of Primary Liver Cancer.
Radiologically confirmed portal vein tumor thrombus (PVTT), classified as Cheng type I-IV.
No prior systemic or local treatment directed at PVTT, including targeted therapy, immunotherapy, or systemic chemotherapy.
ECOG performance status ≥2.
Child-Pugh score ≥8.
Severe dysfunction of major organs, including the heart, liver, or kidneys.
Prior targeted therapy, immunotherapy, radiotherapy, systemic chemotherapy, or other anticancer treatment.
Single group
Iparomlimab and Tuvonralimab (QL1706)
DrugIparomlimab and tuvonralimab (QL1706) will be administered intravenously at 7.5 mg/kg on Day 1 of each 3-week cycle. Each infusion will be administered over 30-60 minutes. Treatment will continue for up to 2 years or until disease progression, unacceptable toxicity, or another protocol-defined reason for discontinuation.
Lenvatinib
DrugLenvatinib will be administered orally once daily at 8 mg for participants weighing \<60 kg and 12 mg for participants weighing ≥60 kg. During HAIC treatment, lenvatinib will be withheld for 3 days before HAIC and for 7 days after HAIC. The interruption period may be extended at the investigator's discretion based on the participant's clinical condition and laboratory findings. Lenvatinib will continue for up to 2 years or until disease progression, unacceptable toxicity, or another protocol-defined reason for discontinuation.
Radiotherapy
RadiationExternal beam radiotherapy directed at the portal vein tumor thrombus (PVTT) will be initiated within 7 days after the first administration of QL1706. The radiation target will include the PVTT. Gross tumor volume will be delineated based on the venous or delayed phase of contrast-enhanced imaging, and a planning target volume margin of approximately 5-15 mm will be applied according to the protocol. SBRT will be delivered at a total dose of 18-40 Gy with 3-6 Gy per fraction.
hepatic arterial infusion chemotherapy (HAIC)
Procedure/SurgeryHAIC will be initiated during Cycle 2 of systemic therapy. Using a modified Seldinger technique, a catheter will be selectively placed in the main tumor-feeding hepatic artery for administration of FOLFOX chemotherapy. HAIC will be repeated every 3 weeks for up to 4 cycles, with the number of cycles adjusted according to the participant's clinical condition
Progression-Free Survival (PFS)
Progression-free survival is defined as the time from the first administration of study treatment to the first documented radiographic disease progression, as assessed by the investigator according to mRECIST, or death from any cause, whichever occurs first.
Objective Response Rate (ORR)
ORR is defined as the proportion of participants who achieve a confirmed complete response (CR) or partial response (PR), as assessed by the investigator according to mRECIST.
Overall Survival (OS)
Overall survival is defined as the time from the first administration of study treatment to death from any cause.
Incidence and Severity of Adverse Events
The incidence and severity of adverse events will be assessed and graded according to NCI CTCAE version 5.0.
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Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Lead sponsor
Qilu Pharmaceutical Co., Ltd.
Collaborator
