Lparomlimab and Tuvonralimab Injection in Combination With TACE and Lenvatinib in the Treatment of Second-Line Therapy for Unresectable Intermediate-to-Advanced Hepatocellular Carcinoma

A Single-Arm, Single-Center Clinical Study Evaluating the Efficacy and Safety of Lparomlimab and Tuvonralimab Injection in Combination With TACE and Lenvatinib as Second-Line Therapy for Unresectable Intermediate-to-Advanced Hepatocellular Carcinoma

Major objectives To evaluate the efficacy of lparomlimab and Tuvonralimab injection (QL1706, an Anti-PD-1/ CTLA-4 Combined Antibody) in combination with TACE and lenvatinib as second-line therapy in patients with unresectable intermediate-to-advanced hepatocellular carcinoma.

Study Overview

• Status: Recruiting
• Conditions: HCC
• Intervention / Treatment: Drug: lparomlimab and Tuvonralimab Injection in Combination with TACE and Lenvatinib

Detailed Description

This single-arm, single-center clinical study aims to evaluate the efficacy and safety of lparomlimab and Tuvonralimab injection (QL1706, an Anti-PD-1/ CTLA-4 Combined Antibody) in combination with TACE and lenvatinib as second-line therapy in patients with unresectable intermediate-to-advanced hepatocellular carcinoma. This study consists of three phases: screening, treatment, and follow-up. Efficacy evaluation and safety monitoring should be performed throughout the study.

• Study Type: Interventional
• Enrollment (Estimated): 29
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tongguo Si, Doctor; Phone Number: +86 18526812877; Email: 18526812877@163.com

Study Locations

• China
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300000
      • Recruiting
      • Tianjin Medical University Cancer Institute and Hospital
      • Contact: Tongguo Si; Phone Number: 18526812877; Email: 18526812877@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Comprehension and voluntary signing of the study's informed consent form;
• Age ≥18 years, any gender;
• Histologically or clinically confirmed hepatocellular carcinoma;
• Documented failure or intolerance to first-line therapy with PD-1/PD-L1 inhibitor plus bevacizumab;
• ECOG performance status 0-2;
• Child-Pugh class A or class B (score ≤7) without hepatic encephalopathy history;
• Life expectancy ≥3 months;
• At least one measurable target lesion confirmed by screening imaging per RECIST v1.1;
• Adequate organ and bone marrow function within 7 days prior to initial study treatment;

• Active HBV/HCV infection requires ongoing antiviral therapy; k.Fertile patients must use highly effective contraception with partners during treatment and ≥180 days post-last dose.

  2.Exclusion Criteria:

• Inability to comply with the study protocol or procedures;
• Histologically/cytologically confirmed fibrolamellar HCC, sarcomatoid HCC, cholangiocarcinoma, or mixed hepatocellular-cholangiocarcinoma;
• History of liver transplantation or planned transplantation;
• Presence of central nervous system metastases and/or leptomeningeal carcinomatosis;
• Baseline imaging showing Vp4 portal vein tumor thrombosis;
• Hypersensitivity to any study drug components or history of severe allergic reactions;
• Concurrent HBV and HCV co-infection;
• Clinically significant ascites requiring intervention during screening;
• Concurrent use of other investigational drugs or participation in another clinical trial within 4 weeks prior to enrollment;
• Esophageal/gastric variceal bleeding due to portal hypertension within 6 months before treatment initiation, or high-risk varices on endoscopy within 3 months;
• Current interstitial lung disease (ILD), history of steroid-required ILD, or other pulmonary fibrosis/organizing pneumonia affecting immune-related pulmonary toxicity assessment;
• Uncontrolled hypertension (SBP≥160 mmHg and/or DBP≥100 mmHg despite medication), coronary artery disease, arrhythmias, or heart failure (NYHA Class ≥II);
• Uncontrolled clinically significant infections requiring IV antimicrobial therapy;
• Proteinuria ≥2+ (≥1.0g/24h);
• History of hemorrhagic tendency regardless of severity within 2 months prior to enrollment;
• Arterial/venous thromboembolic events within 12 months before treatment initiation (e.g., cerebrovascular accident including TIA);
• Acute myocardial infarction, acute coronary syndrome, or CABG within 6 months before treatment;
• Unhealed fractures or chronic non-healing wounds;
• Coagulopathy, bleeding diathesis, or current therapeutic anticoagulation;
• Other malignancies within 5 years except curatively resected basal/squamous cell skin carcinoma or cervical carcinoma in situ;
• Active autoimmune disease or autoimmune disease history requiring immunosuppression within 4 weeks prior to enrollment;
• Prior allogeneic bone marrow or solid organ transplantation;
• Investigator assessment of ineligibility based on medical/safety reasons.

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: lparomlimab and Tuvonralimab Injection in Combination with TACE and Lenvatinib

Drug: lparomlimab and Tuvonralimab Injection in Combination with TACE and Lenvatinib; lparomlimab and Tuvonralimab Injection (QL1706): 7.5 mg/kg, q3w; Lenvatinib: 8 mg once daily for patients weighing <60 kg, or 12 mg once daily for those weighing ≥60 kg, administered orally, continuous daily dosing； TACE: Administered 4-6 times, using a combination of anthracyclines, lipiodol, and microspheres. The procedure should be performed within one week before or after QL1706 administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first.	up to 12 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on investigator assessment.	up to 12 month
Overall survival	OS was defined as the time from the first dose of study drug to death due to any cause.	up to 36 month
Disease Control Rate	DCR was defined as the percentage of participants in the analysis population who have CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage for PR nor sufficient increase for PD [at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm.	up to 12 month
Duration of Response	For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 by investigator assessment, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first.	up to 12 month
Adverse Events	An AE was defined as any untoward medical occurrence in a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment.	up to 36 month

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2025
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2029

Study Registration Dates

• First Submitted: July 13, 2025
• First Submitted That Met QC Criteria: July 27, 2025
• First Posted (Actual): August 1, 2025

Study Record Updates

• Last Update Posted (Estimated): August 29, 2025
• Last Update Submitted That Met QC Criteria: August 22, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Lenvatinib; TACE; Iparomlimab and Tuvonralimab Injection
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; lenvatinib
• Other Study ID Numbers: EC-2025-0041

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