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)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Major Pathological Response (MPR) rate
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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-
- •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.
排除标准
- •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.
研究组 & 干预措施
Experimental group
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)
干预措施: Radical surgery (Procedure)
Experimental group
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)
干预措施: TACE treatment (Procedure)
Experimental group
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)
干预措施: Iparomlimab and Tuvonralimab Injection (QL1706) (Drug)
Experimental group
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)
干预措施: Lenvatinib (Drug)
结局指标
主要结局
Major Pathological Response (MPR) rate
时间窗: 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.
次要结局
- 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)
- Recurrence-Free Survival (RFS)(3-year)
- Overall Survival (OS)(3-year)
- Adverse event (AE)(3-year)
研究者
Xuehao Wang
professor
The First Affiliated Hospital with Nanjing Medical University