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

NCT07131501 | Not Yet Recruiting Phase 2

• 1 other identifier: 2025-SR-348
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatocellular Carcinoma; Immunotherapy; Preoperative; PD-1; CTLA-4

Outcome Measures

Primary Outcomes (1)

• Major Pathological Response (MPR) rate

  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.

  60-day

Secondary Outcomes (8)

• Pathological Complete Response (pCR) rate

  60-day

• R0 resection rate

  60-day

• Objective Response Rate (ORR)

  6-month

• Disease Control Rate (DCR)

  6-month

• Event-Free Survival (EFS)

  3-year

Study Arms (1)

Experimental group

EXPERIMENTAL

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)

Procedure: Radical surgery; Procedure: TACE treatment; Drug: Iparomlimab and Tuvonralimab Injection (QL1706); Drug: Lenvatinib

Interventions

Radical surgery PROCEDURE

Radical surgery

Experimental group

TACE treatment PROCEDURE

TACE treatment (cTACE, Idarubicin): Preoperative: 1 session; Postoperative: 1 session.

Experimental group

Iparomlimab and Tuvonralimab Injection (QL1706) DRUG

Iparomlimab and Tuvonralimab Injection (QL1706): 7.5 mg/kg, intravenous infusion, Day 1 of each cycle, Q3W. Neoadjuvant: 2 cycles; Adjuvant: up to 17 cycles.

Experimental group

Lenvatinib DRUG

Lenvatinib: 8mg (body weight \<60kg) or 12mg (body weight ≥60kg), orally (PO), once daily (QD), Q3W. Consistent daily timing. Neoadjuvant: 2 cycles.

Experimental group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily participate, sign ICF, demonstrate good expected compliance, and be willing to cooperate with follow-up.
• Age 18-75 years, any gender.
• HCC diagnosis confirmed by histopathology, cytology, or imaging.
• 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.
• For CNLC Ib-IIa subjects, presence of at least ONE high-risk recurrence factor.
• 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.
• Child-Pugh class A.
• ECOG PS score 0-1.
• Expected survival ≥12 months.
• Adequate organ function within 7 days prior to study intervention.
• For subjects with HBV infection.
• 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.
• 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.

You may not qualify if:

• 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.
• 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.
• 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.
• Systemic immunosuppressive therapy (\>10 mg/day prednisone equivalent) within 2 weeks prior to intervention.
• 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).
• Primary or acquired immunodeficiency.
• 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.
• Significant bleeding symptoms or predisposition within 6 months prior. If baseline fecal occult blood positive, repeat test; if still positive, requires gastroscopy.
• Known hereditary/acquired bleeding/thrombotic diathesis. Current therapeutic-dose anticoagulants/thrombolytics (prophylactic low-dose aspirin allowed).
• Arterial thromboembolic events within 6 months prior.
• Poorly controlled cardiac disease.
• Hypertension uncontrolled by medication (average SBP ≥140 mmHg or DBP ≥90 mmHg on ≥2 readings). History of hypertensive crisis or encephalopathy.
• Major vascular disease within 6 months prior.
• Serious unhealed wounds, active ulcers, or untreated fractures.
• Major surgery within 4 weeks prior or anticipated major surgery during study.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (1)

The First Affiliated Hospital with Nanjing Medical University

Nanjing, Jiangsu, 210029, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Diabetes Mellitus, Insulin-Dependent, 12

Interventions

lenvatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Xuehao Wang

  The First Affiliated Hospital with Nanjing Medical University

  STUDY CHAIR

• Yongxiang Xia

  The First Affiliated Hospital with Nanjing Medical University

  STUDY DIRECTOR

Central Study Contacts

Xuehao Wang

CONTACT

86-025-68303211; Wangxh@njmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: August 13, 2025
• First Posted: August 20, 2025
• Study Start: August 11, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): August 31, 2029
• Last Updated: August 20, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)