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

Официальное название

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

Обзор

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.

Подробное описание

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).

Вмешательства

• Процедура Radical surgery
  Radical surgery
• Процедура TACE treatment
  TACE treatment (cTACE, Idarubicin): Preoperative: 1 session; Postoperative: 1 session.
• Препарат Iparomlimab and Tuvonralimab Injection (QL1706)
  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.
• Препарат Lenvatinib
  Lenvatinib: 8mg (body weight \<60kg) or 12mg (body weight ≥60kg), orally (PO), once daily (QD), Q3W. Consistent daily timing. Neoadjuvant: 2 cycles.

Первичные конечные точки

• Major Pathological Response (MPR) rate [Срок оценки: 60-day]

Вторичные конечные точки (8)

• Pathological Complete Response (pCR) rate [Срок оценки: 60-day]
• R0 resection rate [Срок оценки: 60-day]
• Objective Response Rate (ORR) [Срок оценки: 6-month]
• Disease Control Rate (DCR) [Срок оценки: 6-month]
• Event-Free Survival (EFS) [Срок оценки: 3-year]
• Recurrence-Free Survival (RFS) [Срок оценки: 3-year]
• Overall Survival (OS) [Срок оценки: 3-year]
• Adverse event (AE) [Срок оценки: 3-year]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.
• Inability to swallow pills, malabsorption syndrome, or GI condition affecting absorption.
• 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.
• Strong CYP3A4 inducers within 2 weeks prior or strong CYP3A4 inhibitors within 1 week prior.
• Known hypersensitivity to any study drug or excipient.
• Participation in another investigational drug study within 4 weeks prior.
• Pregnancy or lactation.
• Any other condition deemed unsuitable by the investigator.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The First Affiliated Hospital with Nanjing Medical University — Нанкин

Идентификаторы

NCT: NCT07131501 · 2025-SR-348

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗