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

Official title

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

Overview

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.

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.

Interventions

• 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.

Primary outcome measures

• Progression-Free Survival (PFS) [Time frame: up to 12 month]

Secondary outcome measures (5)

• Objective response rate [Time frame: up to 12 month]
• Overall survival [Time frame: up to 36 month]
• Disease Control Rate [Time frame: up to 12 month]
• Duration of Response [Time frame: up to 12 month]
• Adverse Events [Time frame: up to 36 month]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Tianjin Medical University Cancer Institute and Hospital — Tianjin

Identifiers

NCT: NCT07099274 · EC-2025-0041

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗