Iparomlimab and Tuvonralimab With Lenvatinib, Radiotherapy, and HAIC for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus

NCT07776080 | Recruiting Phase 2

• 1 other identifier: UHCC-A1c
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HCC - Hepatocellular Carcinoma

Keywords

Hepatocellular Carcinoma; Portal Vein Tumor Thrombus; Lenvatinib; Iparomlimab and Tuvonralimab; Radiotherapy; Hepatic Arterial Infusion Chemotherapy

Outcome Measures

Primary Outcomes (1)

• 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.

  From first administration of study treatment to radiographic disease progression or death from any cause, whichever occurs first, up to 24 months

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  From first administration of study treatment to disease progression or the last tumor assessment, up to 24 months

• Overall Survival (OS)

  From first administration of study treatment to death from any cause, up to 24 months

• Incidence and Severity of Adverse Events

  From informed consent through 30 days after the last administration of study treatment

Study Arms (1)

Treatment group

EXPERIMENTAL

Participants will receive iparomlimab and tuvonralimab (QL1706) at 7.5 mg/kg intravenously on Day 1 every 3 weeks, together with oral lenvatinib once daily (8 mg for body weight \<60 kg and 12 mg for body weight ≥60 kg). PVTT-directed radiotherapy will be initiated within 7 days after the first QL1706 administration. HAIC with a FOLFOX regimen will be added from Cycle 2 and repeated every 3 weeks for up to 4 cycles. Lenvatinib will be withheld for 3 days before and 7 days after each HAIC procedure. QL1706 and lenvatinib will continue for up to 2 years or until disease progression, unacceptable toxicity, or another protocol-defined reason for discontinuation.

Drug: Iparomlimab and Tuvonralimab (QL1706); Drug: Lenvatinib; Radiation: Radiotherapy; Procedure: hepatic arterial infusion chemotherapy (HAIC)

Interventions

Iparomlimab and Tuvonralimab (QL1706) DRUG

Iparomlimab 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.

Treatment group

Lenvatinib DRUG

Lenvatinib 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.

Treatment group

Radiotherapy RADIATION

External 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.

Treatment group

hepatic arterial infusion chemotherapy (HAIC) PROCEDURE

HAIC 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

Treatment group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Child-Pugh class A or B with a Child-Pugh score ≤7.
• Considered unsuitable for curative surgery or liver transplantation after multidisciplinary evaluation, but suitable for radiotherapy.
• Adequate organ function, including: WBC ≥3.0 × 10⁹/L; PLT ≥50 × 10⁹/L; hemoglobin ≥80 g/L; ALT ≤5 × ULN; AST ≤5 × ULN; total bilirubin ≤3 × ULN; albumin ≥28 g/L; and creatinine clearance ≥80 mL/min.
• At least one measurable lesion according to mRECIST.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Life expectancy \>3 months.
• No history of abdominal radiotherapy.
• Women of childbearing potential must use effective contraception beginning at least 1 month before screening and throughout the study until the protocol-specified period after study completion.
• Willing and able to comply with study follow-up until death, study completion, or study termination.

You may not qualify if:

• 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.
• Known hypersensitivity or allergic reaction to any component of the study treatment.
• History of organ transplantation or autologous/allogeneic stem cell transplantation.
• Currently receiving chronic systemic immunotherapy or hormonal therapy other than physiologic replacement therapy.
• Any unstable systemic disease, including active infection; uncontrolled severe hypertension; unstable angina; new-onset angina within the previous 3 months; congestive heart failure of NYHA class II or higher; myocardial infarction within the previous 6 months; severe cardiac arrhythmia requiring medication; gastrointestinal bleeding within the previous 1 month; or active bleeding tendency.
• Concurrent other malignancy that has not been cured, except carcinoma in situ at another site.
• Any disease, metabolic disorder, physical examination finding, or laboratory abnormality that, in the investigator's judgment, suggests a contraindication to the study treatment or a high risk of treatment-related complications.
• Evidence of acute or active hepatitis B or hepatitis C infection, including HBV-DNA \>2,000 IU/mL or HCV-RNA \>1,000 copies/mL.
• Pregnancy or breastfeeding.
• Any other unfavorable medical or psychiatric condition that, in the investigator's judgment, may affect protocol compliance or evaluation of study endpoints and makes the participant unsuitable for the study.
• Lack of legal capacity or limited legal capacity.
• Other contraindications to radiotherapy or targeted/immunotherapy.

Sponsors & Collaborators

• Qilu Pharmaceutical Co., Ltd.: collaborator
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead

Study Sites (1)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Wuhan, Hubei, 430022, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

lenvatinib; Radiotherapy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Jun Xue, Doctor

CONTACT

027-83262682; junxue_xh@hust.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2026
• First Posted: August 20, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2028
• Last Updated: September 15, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)