QL1706 (iparomlimab + tuvonralimab) with TACE and lenvatinib for second-line treatment of unresectable intermediate-to-advanced liver cancer

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

This test will try whether adding QL1706 (iparomlimab plus tuvonralimab) to TACE and lenvatinib helps people with unresectable intermediate-to-advanced hepatocellular carcinoma who progressed after PD-1/PD-L1 plus bevacizumab.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 29 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Tianjin Medical University Cancer Institute and Hospital (Academic / other)
• Drugs / interventions: bevacizumab, lparomlimab, Tuvonralimab, lenvatinib
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT07099274 on ClinicalTrials.gov

What this trial studies

This single-arm, single-center Phase 2 trial gives participants the combined antibody QL1706 (iparomlimab plus tuvonralimab) together with transarterial chemoembolization (TACE) and oral lenvatinib as second-line therapy for unresectable intermediate-to-advanced hepatocellular carcinoma. The protocol includes screening, a treatment period with scheduled QL1706 dosing plus TACE and continuous lenvatinib, and a follow-up phase for efficacy and safety monitoring. Eligible patients must have failed or been intolerant to first-line PD-1/PD-L1 inhibitor plus bevacizumab and have at least one measurable lesion per RECIST v1.1. Tumor response, progression-free and overall survival, and adverse events will be recorded throughout the trial.

Who should consider this trial

Good fit: Ideal candidates are adults with unresectable intermediate-to-advanced hepatocellular carcinoma who progressed on or could not tolerate first-line PD-1/PD-L1 plus bevacizumab, have ECOG performance status 0–2, Child-Pugh A or B (score ≤7), and at least one measurable lesion.

Not a fit: Patients with excluded histologies (fibrolamellar, sarcomatoid, cholangiocarcinoma, or mixed tumors), poor liver function (Child-Pugh >7), severe comorbidities, or those unable to undergo TACE or systemic therapy are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, the combination could increase tumor response rates and prolong progression-free and overall survival for patients who have limited second-line options.

How similar studies have performed: Combining immunotherapy with locoregional therapy and tyrosine kinase inhibitors has shown promising signals in other early trials, but the specific QL1706 plus TACE and lenvatinib regimen is novel and not yet proven.

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.

Where this trial is running

Tianjin, Tianjin Municipality

• Tianjin Medical University Cancer Institute and Hospital — Tianjin, Tianjin Municipality, China (Recruiting)

Study contacts

• Study coordinator: Tongguo Si, Doctor

Conditions HCC; Iparomlimab and Tuvonralimab Injection; TACE; Lenvatinib