Lparomlimab and Tuvonralimab Injection in Combination With TACE and Lenvatinib in the Treatment of Second-Line Therapy for Locally Advanced or Metastatic Clear Cell Renal Cell Carcinoma Following Failure of First-Line Systemic Therapy

Not Applicable

Not yet recruiting

• Conditions: HCC
• Interventions: Drug: lparomlimab and Tuvonralimab Injection in Combination with TACE and Lenvatinib

• Registration Number: NCT07099274
• Lead Sponsor: Tianjin Medical University Cancer Institute and Hospital

Brief Summary

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.

Study Timeline

• Status Verified: 2025-07
• Study First Submitted: 2025-07-13
• Study First Submitted QC: 2025-07-27
• Last Update Submitted: 2025-07-27
• Study First Posted: 2025-08-01
• Last Update Posted: 2025-08-01
• Study Start: 2025-08-15
• Primary Completion: 2027-12-30
• Study Completion: 2029-12-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

1. Comprehension and voluntary signing of the study's informed consent form;
2. Age ≥18 years, any gender;
3. Histologically or clinically confirmed hepatocellular carcinoma;
4. Documented failure or intolerance to first-line therapy with PD-1/PD-L1 inhibitor plus bevacizumab;
5. ECOG performance status 0-2;
6. Child-Pugh class A or class B (score ≤7) without hepatic encephalopathy history;
7. Life expectancy ≥3 months;
8. At least one measurable target lesion confirmed by screening imaging per RECIST v1.1;
9. Adequate organ and bone marrow function within 7 days prior to initial study treatment;
10. Active HBV/HCV infection requires ongoing antiviral therapy;
11. Fertile patients must use highly effective contraception with partners during treatment and ≥180 days post-last dose.

Exclusion Criteria

1. Inability to comply with the study protocol or procedures;
2. Histologically/cytologically confirmed fibrolamellar HCC, sarcomatoid HCC, cholangiocarcinoma, or mixed hepatocellular-cholangiocarcinoma;
3. History of liver transplantation or planned transplantation;
4. Presence of central nervous system metastases and/or leptomeningeal carcinomatosis;
5. Baseline imaging showing Vp4 portal vein tumor thrombosis;
6. Hypersensitivity to any study drug components or history of severe allergic reactions;
7. Concurrent HBV and HCV co-infection;
8. Clinically significant ascites requiring intervention during screening;
9. Concurrent use of other investigational drugs or participation in another clinical trial within 4 weeks prior to enrollment;
10. Esophageal/gastric variceal bleeding due to portal hypertension within 6 months before treatment initiation, or high-risk varices on endoscopy within 3 months;
11. Current interstitial lung disease (ILD), history of steroid-required ILD, or other pulmonary fibrosis/organizing pneumonia affecting immune-related pulmonary toxicity assessment;
12. Any of the following concurrent conditions:

(1) Uncontrolled hypertension (SBP≥160 mmHg and/or DBP≥100 mmHg despite medication), coronary artery disease, arrhythmias, or heart failure (NYHA Class ≥II) (2) Uncontrolled clinically significant infections requiring IV antimicrobial therapy (3) Proteinuria ≥2+ (≥1.0g/24h) (4) History of hemorrhagic tendency regardless of severity within 2 months prior to enrollment (5) Arterial/venous thromboembolic events within 12 months before treatment initiation (e.g., cerebrovascular accident including TIA) (6) Acute myocardial infarction, acute coronary syndrome, or CABG within 6 months before treatment (7) Unhealed fractures or chronic non-healing wounds (8) Coagulopathy, bleeding diathesis, or current therapeutic anticoagulation 13. Other malignancies within 5 years except curatively resected basal/squamous cell skin carcinoma or cervical carcinoma in situ; 14. Active autoimmune disease or autoimmune disease history requiring immunosuppression within 4 weeks prior to enrollment; 15. Prior allogeneic bone marrow or solid organ transplantation; 16. Investigator assessment of ineligibility based on medical/safety reasons.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
lparomlimab and Tuvonralimab Injection in Combination with TACE and Lenvatinib	lparomlimab and Tuvonralimab Injection in Combination with TACE and Lenvatinib	lparomlimab and Tuvonralimab Injection in Combination with TACE and Lenvatinib

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS)	up to 12 month	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.

Secondary Outcome Measures

Name	Time	Method
Overall survival	up to 36 month	OS was defined as the time from the first dose of study drug to death due to any cause.
Objective response rate	up to 12 month	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.
Disease Control Rate	up to 12 month	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.
Duration of Response	up to 12 month	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.
Adverse Events	up to 36 month	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.

Trial Locations

Locations (1)

Tianjin Medical University Cancer Institute and Hospital; 🇨🇳 Tianjin, Tianjin, China