A Single-Arm, Multicenter, Exploratory Clinical Study of TACE Combined With Iparomlimab and Tuvonralimab Injection (QL1706) and Lenvatinib for Perioperative Treatment of Resectable Hepatocellular Carcinoma

Not Applicable

Not yet recruiting

• Conditions: Hepatocellular Carcinoma; Immunotherapy; Preoperative; PD-1; CTLA-4
• Interventions: Procedure: Radical surgery; Procedure: TACE treatment; Drug: Iparomlimab and Tuvonralimab Injection (QL1706); Drug: Lenvatinib

• Registration Number: NCT07131501
• Lead Sponsor: The First Affiliated Hospital with Nanjing Medical University

Brief Summary

This is a single-arm, multicenter, exploratory clinical study evaluating the efficacy and safety of TACE combined with Iparomlimab and Tuvonralimab Injection (QL1706) and lenvatinib for perioperative treatment of resectable HCC (CNLC IIb-IIIa excluding Vp3/Vp4 or CNLC Ib-IIa with high-risk recurrence factors). Eligible subjects providing written informed consent will receive study treatment. The primary endpoint is MPR rate.

Detailed Description

This is a single-arm, multicenter, exploratory clinical study evaluating the efficacy and safety of TACE combined with Iparomlimab and Tuvonralimab Injection (QL1706) and lenvatinib for perioperative treatment of resectable HCC (CNLC IIb-IIIa excluding Vp3/Vp4 or CNLC Ib-IIa with high-risk recurrence factors). Eligible subjects providing written informed consent will receive study treatment. The primary endpoint is MPR rate.

To standardize TACE efficacy and tolerability, conventional lipiodol-based TACE (cTACE) with idarubicin as the chemotherapeutic agent is employed. The treatment sequence is: Preoperative TACE (1 session) → Iparomlimab and Tuvonralimab Injection (QL1706) + Lenvatinib (Q3W, 2 cycles) → Radical surgery ± intraoperative microwave ablation → Postoperative TACE (1 session) → Iparomlimab and Tuvonralimab Injection (QL1706) (Q3W, ≤17 cycles).

Safety Visits: Occur at screening, pre-TACE, Cycle D1 of neoadjuvant Iparomlimab and Tuvonralimab Injection (QL1706), pre-surgery, pre-postoperative TACE, Cycle D1 of adjuvant Iparomlimab and Tuvonralimab Injection (QL1706), and end of treatment.

Survival Follow-up: Every 12 weeks after safety visits via clinic visit or phone call to collect survival status and subsequent anti-cancer therapy until death, loss to follow-up, sponsor termination, or study completion.

Imaging Assessment: All lesions assessed per RECIST v1.1 and mRECIST. Consistent scanning parameters are required.

Pathological Assessment: Post-surgery assessment of pathological response (MPR, pCR rates) and resection margin status (R0).

Study Timeline

• Status Verified: 2025-08
• Study Start: 2025-08-11
• Study First Submitted: 2025-08-13
• Study First Submitted QC: 2025-08-13
• Last Update Submitted: 2025-08-13
• Study First Posted: 2025-08-20
• Last Update Posted: 2025-08-20
• Primary Completion: 2026-09-30
• Study Completion: 2029-08-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

1. Voluntarily participate, sign ICF, demonstrate good expected compliance, and be willing to cooperate with follow-up.
2. Age 18-75 years, any gender.
3. HCC diagnosis confirmed by histopathology, cytology, or imaging.
4. Resectable HCC staged as CNLC IIb-IIIa (excluding Vp3 and Vp4) or CNLC Ib-IIa with high-risk recurrence factors, confirmed by multidisciplinary liver surgery expert panel.
5. For CNLC Ib-IIa subjects, presence of at least ONE high-risk recurrence factor.
6. No prior systemic therapy for HCC (chemotherapy, targeted therapy, immunotherapy, etc.). Subjects with prior curative surgery or ablation are eligible only if recurrence occurred >2 years post-resection. Subjects with prior other local therapies are excluded.
7. Child-Pugh class A.
8. ECOG PS score 0-1.
9. Expected survival ≥12 months.
10. Adequate organ function within 7 days prior to study intervention.
11. For subjects with HBV infection.
12. Women of childbearing potential: Must agree to abstinence or use highly effective contraception from ICF signing until ≥120 days after last study drug dose. Negative pregnancy test within 7 days prior to intervention. Not breastfeeding.
13. Male subjects with WOCBP partners: Must agree to abstinence or use highly effective contraception from ICF signing until ≥120 days after last study drug dose. Must not donate sperm during this period. Males with pregnant partners must use condoms.

Exclusion Criteria

1. Known intrahepatic cholangiocarcinoma, sarcomatoid HCC, mixed carcinoma (>30% ICC component), or fibrolamellar carcinoma. Active malignancy other than HCC within 5 years or concurrently. Cured localized cancers are eligible.
2. Current or history of interstitial lung disease/pneumonitis requiring steroids, or other active lung disease potentially interfering with immune-related pulmonary toxicity evaluation/management, or active pneumonia/severe impaired pulmonary function on screening CT. Active tuberculosis.
3. Active autoimmune disease or history of autoimmune disease with potential recurrence. Vitiligo, psoriasis, alopecia not requiring systemic therapy, controlled Type I diabetes on insulin, or childhood asthma resolved in adulthood without intervention are eligible. Asthma requiring bronchodilators is excluded.
4. Systemic immunosuppressive therapy (>10 mg/day prednisone equivalent) within 2 weeks prior to intervention.
5. Active infection, unexplained fever ≥38.5°C within 1 week prior, or baseline WBC >15 × 10⁹/L. Therapeutic antibiotics (IV/oral) within 2 weeks prior (prophylactic IV antibiotics ≤48h duration allowed).
6. Primary or acquired immunodeficiency.
7. Live attenuated vaccine within 4 weeks prior to intervention or anticipated need during study or within 60 days after last Iparomlimab and Tuvonralimab Injection dose.
8. Significant bleeding symptoms or predisposition within 6 months prior. If baseline fecal occult blood positive, repeat test; if still positive, requires gastroscopy.
9. Known hereditary/acquired bleeding/thrombotic diathesis. Current therapeutic-dose anticoagulants/thrombolytics (prophylactic low-dose aspirin allowed).
10. Arterial thromboembolic events within 6 months prior.
11. Poorly controlled cardiac disease.
12. Hypertension uncontrolled by medication (average SBP ≥140 mmHg or DBP ≥90 mmHg on ≥2 readings). History of hypertensive crisis or encephalopathy.
13. Major vascular disease within 6 months prior.
14. Serious unhealed wounds, active ulcers, or untreated fractures.
15. Major surgery within 4 weeks prior or anticipated major surgery during study.
16. Inability to swallow pills, malabsorption syndrome, or GI condition affecting absorption.
17. Bowel obstruction or related symptoms/signs within 6 months prior requiring parenteral support/feeding. Subjects with prior resolved obstruction treated definitively (surgically) may be eligible after assessment.
18. Strong CYP3A4 inducers within 2 weeks prior or strong CYP3A4 inhibitors within 1 week prior.
19. Known hypersensitivity to any study drug or excipient.
20. Participation in another investigational drug study within 4 weeks prior.
21. Pregnancy or lactation.
22. Any other condition deemed unsuitable by the investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental group	Radical surgery	Preoperative TACE (1 session) → Iparomlimab and Tuvonralimab Injection (QL1706) + Lenvatinib (Q3W, 2 cycles) → Radical surgery ± intraoperative microwave ablation → Postoperative TACE (1 session) → Iparomlimab and Tuvonralimab Injection (QL1706) (Q3W, ≤17 cycles)
Experimental group	TACE treatment	Preoperative TACE (1 session) → Iparomlimab and Tuvonralimab Injection (QL1706) + Lenvatinib (Q3W, 2 cycles) → Radical surgery ± intraoperative microwave ablation → Postoperative TACE (1 session) → Iparomlimab and Tuvonralimab Injection (QL1706) (Q3W, ≤17 cycles)
Experimental group	Iparomlimab and Tuvonralimab Injection (QL1706)	Preoperative TACE (1 session) → Iparomlimab and Tuvonralimab Injection (QL1706) + Lenvatinib (Q3W, 2 cycles) → Radical surgery ± intraoperative microwave ablation → Postoperative TACE (1 session) → Iparomlimab and Tuvonralimab Injection (QL1706) (Q3W, ≤17 cycles)
Experimental group	Lenvatinib	Preoperative TACE (1 session) → Iparomlimab and Tuvonralimab Injection (QL1706) + Lenvatinib (Q3W, 2 cycles) → Radical surgery ± intraoperative microwave ablation → Postoperative TACE (1 session) → Iparomlimab and Tuvonralimab Injection (QL1706) (Q3W, ≤17 cycles)

Primary Outcome Measures

Name	Time	Method
Major Pathological Response (MPR) rate	60-day	Proportion of subjects achieving MPR (defined as ≤10% residual viable tumor cells in the original tumor bed after neoadjuvant therapy, i.e., ≥90% necrosis) among all enrolled subjects.

Secondary Outcome Measures

Name	Time	Method
Pathological Complete Response (pCR) rate	60-day	Proportion of subjects achieving pCR (defined as no residual viable tumor cells in the original tumor bed after neoadjuvant therapy) among all enrolled subjects.
R0 resection rate	60-day	R0 resection rate
Objective Response Rate (ORR)	6-month	Proportion of subjects achieving Complete Response (CR) or Partial Response (PR) among all enrolled subjects (assessed by investigators per RECIST v1.1 and mRECIST).
Disease Control Rate (DCR)	6-month	Proportion of subjects achieving CR, PR, or Stable Disease (SD) among all enrolled subjects (assessed by investigators per RECIST v1.1 and mRECIST)
Event-Free Survival (EFS)	3-year	Time from the start of neoadjuvant therapy to the first occurrence of any of the following events: disease progression precluding surgery, postoperative recurrence or metastasis, or death from any cause.
Recurrence-Free Survival (RFS)	3-year	(For patients undergoing Radical surgery only) Time from the date of Radical surgery to tumor recurrence or death from any cause, whichever occurs first.
Overall Survival (OS)	3-year	Time from the start of neoadjuvant therapy to death from any cause.
Adverse event (AE)	3-year	Adverse events (AEs), Serious Adverse events (SAEs), surgery related safety.

Trial Locations

Locations (1)

The First Affiliated Hospital with Nanjing Medical University; 🇨🇳 Nanjing, Jiangsu, China