Iparomlimab/Tuvonralimab Plus SBRT and Lenvatinib for Perioperative Treatment of Potentially Resectable Intermediate-Stage HCC

A Single-Arm, Single-Center Clinical Trial Evaluating Efficacy and Safety of Iparomlimab/Tuvonralimab Plus Stereotactic Body Radiation Therapy and Lenvatinib for Perioperative Treatment of Potentially Resectable Intermediate-Stage Hepatocellular Carcinoma

This study aims to evaluate the efficacy and safety of Iparomlimab and Tuvonralimab (the combination antibody) combined with SBRT and Lenvatinib in the perioperative treatment of patients with potentially resectable intermediate-stage hepatocellular carcinoma.. The objective is to explore potential survival benefits for this population and provide patients with more effective treatment options.

Study Overview

• Status: Recruiting
• Conditions: HCC - Hepatocellular Carcinoma
• Intervention / Treatment: Combination product: Iparomlimab/Tuvonralimab plus SBRT and Lenvatinib

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Maobin Meng; Phone Number: 022-23340123; Email: mmeng@tmu.edu.cn
• Study Contact Backup: Name: Tianqiang Song; Phone Number: 022-23340123

Study Locations

• China
  • Tianjin, China
    • Recruiting
    • Tianjin medical university institute & hospital
    • Contact: Maobin Meng; Phone Number: 022-23340123; Email: mmeng@tmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Able to understand and voluntarily sign the informed consent form for this study. · Age ≥18 years old, male and female. · Pathologically or clinically confirmed potentially resectable intermediate-stage hepatocellular carcinoma (stage IIIa). · ECOG performance status of 0-1; · Child-Pugh score <7. · No prior anti-tumor treatment; · Expected survival ≥3 months; · At least one measurable target lesion confirmed by imaging examination during the screening period, according to RECIST v1.1 criteria; · Adequate organ and bone marrow function within 7 days prior to the first administration of study drug.· If HBV or HCV infection is present, the patient must be receiving regular treatment.· Fertile eligible patients must agree to use reliable contraceptive methods with their partner during the trial and for at least 180 days after the last dose of study drug.

Exclusion Criteria:

• Unable to comply with the study protocol or study procedures;· Histologically or cytologically confirmed fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma, combined hepatocellular-cholangiocarcinoma (mixed hepatocellular carcinoma), or other similar types; · Presence of extrahepatic metastatic lesions; · History of liver transplantation, or planned liver transplantation; · Evidence of central nervous system metastasis, and/or patients with carcinomatous meningitis; · History of hypersensitivity to the study drug or its formulation components, or known allergic diathesis; · Co-infection with hepatitis B virus (HBV) and hepatitis C virus (HCV); · Presence of ascites requiring clinical intervention, or uncontrolled pleural effusion, pericardial effusion of moderate or greater amount, etc., as confirmed by screening examinations; · History of esophageal or gastric variceal bleeding due to portal hypertension within 6 months prior to the first dose of study drug, or known severe varices on endoscopy within 3 months prior to the first dose of study drug; · Current interstitial pneumonia or interstitial lung disease, or history of interstitial pneumonia or interstitial lung disease requiring corticosteroid treatment, or other pulmonary fibrosis or organizing pneumonia that may interfere with the assessment and management of immune-related pulmonary toxicity; · Obvious bleeding tendency or other evidence of significant coagulation disorders; · History of severe cardiovascular or cerebrovascular disease; · History of other malignancies within 5 years prior to enrollment, except for radically resected basal cell carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ; · Active autoimmune disease within 4 weeks prior to enrollment, or history of autoimmune disease; · Prior allogeneic bone marrow transplantation or organ transplantation; · Patients considered by the investigator to be unsuitable for enrollment in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Iparomlimab/Tuvonralimab plus SBRT and Lenvatinib

Combination product: Iparomlimab/Tuvonralimab plus SBRT and Lenvatinib; Iparomlimab/Tuvonralimab: Intravenous infusion of 7.5 mg/kg repeated every 21 days as one cycle. Administration for 2-3 cycles before sugery and continuously for one year after surgery. Lenvatinib: orally at a dose of 8 mg once daily (for patients with body weight <60 kg) or 12 mg once daily (for patients with body weight ≥60 kg), and taken continuously for one year after surgery. Stereotactic body radiation therapy: 40-45 Gy/5F, once daily, 1-2 weeks before Iparomlimab/Tuvonralimab. Surgery will be performed within 4-6 weeks after the last dose of conversion therapy, with a maximum of 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of TEAEs	including adverse events and their severity (classified according to CTCAE v5.0), frequency of occurrence, etc.	From date of randomization until the occurrence of adverse events assessed up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of R0 Resection	The proportion of patients in whom the tumor is completely removed with no residual microscopic disease (negative surgical margins).	From date of randomization until the completion of operation assessed about 6 months
Event-Free Survival	The time from randomization to the occurrence of any predefined event, which may include disease progression, recurrence, death, or treatment failure.	From date of randomization until disease progression, recurrence, death, or treatment failure assessed up to 24 months

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): August 15, 2028
• Study Completion (Estimated): August 15, 2028

Study Registration Dates

• First Submitted: August 30, 2026
• First Submitted That Met QC Criteria: August 30, 2026
• First Posted (Actual): September 3, 2026

Study Record Updates

• Last Update Posted (Actual): September 3, 2026
• Last Update Submitted That Met QC Criteria: August 30, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Lenvatinib; Stereotactic body radiation therapy; Iparomlimab/Tuvonralimab
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Investigative Techniques; Therapeutics; Surgical Procedures, Operative; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Radiosurgery; lenvatinib
• Other Study ID Numbers: E20260375

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No