A Clinical Trial of Firsekibart, Tislelizumab, and Lenvatinib in Patients With Unresectable, TP53-Mutated Hepatocellular Carcinoma
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 25
- 主要终点
- Objective Response Rate (ORR) per RECIST v1.1
研究概览
简要总结
This study aims to evaluate the effectiveness and safety of a combination therapy with Fuxinqibai monoclonal antibody, Tislelizumab, and Lenvatinib in patients with advanced, unresectable TP53-mutated hepatocellular carcinoma (HCC) who have previously failed systemic immunotherapy.
Eligible patients will receive:
Fuxinqibai 200 mg IV every 3 weeks Tislelizumab 200 mg IV every 3 weeks Lenvatinib 8 mg (≤60 kg) or 12 mg (>60 kg) orally once daily Treatment will continue until disease progression, unacceptable toxicity, start of a new anticancer therapy, withdrawal of consent, or other protocol-defined reasons. Tumor response will be evaluated by RECIST v1.1 every 6 weeks, and confirmed after 4 weeks if response is observed.
Safety will be monitored through adverse events and laboratory tests, graded according to NCI CTCAE v5.0. After treatment ends, patients will be followed every 6 weeks for tumor assessment and every 12 weeks for survival, until death, loss to follow-up, or withdrawal of consent.
Primary Objective: To assess the objective response rate (ORR) of the combination therapy.
Secondary Objectives: To evaluate overall efficacy, safety, and explore potential biomarkers predicting treatment response.
详细描述
Study Title
Evaluation of Firsekibart Combined with Tirelizumab and Lenvatinib in Patients with Unresectable, Advanced TP53-Mutant Hepatocellular Carcinoma After Progression on Prior Systemic Immunotherapy: An Open-Label, Single-Arm Clinical Study
Brief Summary
This open-label, single-arm study investigates the efficacy and safety of Firsekibart in combination with Tirelizumab and Lenvatinib in adult patients with unresectable, advanced TP53-mutant hepatocellular carcinoma (HCC) who have progressed after prior PD-1/PD-L1-based systemic immunotherapy. The primary objective is to determine the objective response rate (ORR). Secondary objectives include disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety and tolerability, quality of life (QoL), pathological response, patterns of disease progression, and exploration of predictive biomarkers in tumor tissue and blood.
Study Design
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
盲法说明
This is an open-label study; no participants, care providers, investigators, or outcomes assessors are masked
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability to understand and sign written informed consent prior to any study-related procedures.
- •Age ≥18 years at the time of signing informed consent.
- •Histologically or cytologically confirmed advanced or unresectable hepatocellular carcinoma (HCC).
- •Documented disease progression after prior systemic immunotherapy, including at least one PD-(L)1 inhibitor.
- •Confirmed TP53 mutation in fresh liver tumor tissue by central laboratory testing.
- •Determined by liver tumor MDT to be unsuitable for curative surgery (R0 resection not feasible, insufficient normal liver volume, or other criteria).
- •BCLC stage B or C.
- •At least one measurable lesion per RECIST v1.1 confirmed by BICR.
- •ECOG performance status 0-
- •Child-Pugh class A within 7 days prior to randomization.
- •Adequate organ and bone marrow function within 7 days prior to enrollment:
- •ANC ≥1.5×10^9/L, Platelets ≥75×10^9/L, HGB ≥9 g/dL
- •TBIL ≤2×ULN, ALT/AST ≤5×ULN, Albumin ≥28 g/L, ALP ≤5×ULN
- •Creatinine ≤1.5×ULN or CCr ≥50 mL/min, urine protein <2+ (or 24-h urine protein <1 g if baseline ≥2+)
- •INR ≤2.3 or PT prolongation ≤6 sec
- •Expected survival ≥12 weeks.
- •Women of childbearing potential and male participants with partners of childbearing potential must use effective contraception during treatment and for 6 months after last dose.
- •Ability and willingness to comply with study procedures and visits.
排除标准
- •Candidates suitable for local curative therapy.
- •Mixed liver tumors containing sarcomatoid or intrahepatic cholangiocarcinoma components.
- •Hematologic malignancies.
- •History of hepatic encephalopathy or prior liver transplantation.
- •Symptomatic pleural effusion, ascites, or pericardial effusion requiring drainage; asymptomatic small effusions allowed.
- •Active HBV (HBV DNA >2000 IU/mL) or HCV (HCV RNA >10^3 copies/mL) infection; co-infection HBsAg+/HCV Ab+ excluded.
- •CNS metastases.
- •Significant recent variceal bleeding (within 6 months).
- •Life-threatening hemorrhagic events within 3 months.
- •Significant thromboembolic events within 6 months.
- •Use of high-dose aspirin (>325 mg/day) or other platelet inhibitors within 2 weeks prior to first dose.
- •Unresolved grade ≥2 toxicities from prior therapies (excluding hair loss or asymptomatic lab abnormalities).
- •Symptomatic heart failure NYHA II-IV or LVEF <50%.
- •Uncontrolled arrhythmias or congenital long QT syndrome, QTc >500 ms.
- •Active bleeding disorders or on thrombolytic therapy.
- •Recent history of gastrointestinal perforation, fistula, obstruction, or significant bowel disease.
- •Radiotherapy within 3-7 weeks prior to first dose with residual toxicity.
- •History of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-induced lung injury, or severe impaired lung function.
- •Active tuberculosis or treatment for TB within 1 year.
- •HIV infection or active, untreated syphilis.
- •Active or uncontrolled severe infection within 4 weeks prior to first dose.
- •Active autoimmune disease requiring systemic treatment within 2 years. Known primary immunodeficiency.
- •Use of systemic immunosuppressants within 4 weeks prior to first dose (nasal/inhaled steroids at physiologic dose allowed).
- •Receipt of live attenuated vaccines within 4 weeks prior to first dose.
- •Major surgery within 4 weeks prior to first dose, or unhealed wounds. Minor procedures like IV lines excluded.
- •Uncontrolled metabolic disorders or organ/systemic disease posing excess risk.
- •History of other malignancy within 5 years, except curatively treated basal cell carcinoma, squamous cell carcinoma, or in situ carcinoma.
- •Known hypersensitivity to study drugs or formulation components.
- •History of aortic dissection or visceral artery aneurysm.
- •Participation in another clinical trial within 4 weeks prior to first dose.
- •Pregnant or breastfeeding women.
- •Extensive metastatic disease (≥5 lesions) or major vascular invasion.
- •Other acute or chronic diseases, psychiatric conditions, or lab abnormalities deemed by investigator to increase risk or interfere with study.
研究组 & 干预措施
Firsekibart Combined with Tislelizumab and Lenvatinib in Advanced TP53-Mutated Unresectable HCC
articipants will receive Firsekibart 200 mg IV on Day 1 every 3 weeks, followed 1 hour later by Tislelizumab 200 mg IV on Day 1 every 3 weeks, and Lenvatinib orally once daily at 8 mg for patients ≤60 kg or 12 mg for patients >60 kg. Treatment continues until disease progression, unacceptable toxicity, initiation of new anti-tumor therapy, withdrawal of consent, or other protocol-specified discontinuation criteria.
干预措施: Firsekibart + Tislelizumab + Lenvatinib (Drug)
结局指标
主要结局
Objective Response Rate (ORR) per RECIST v1.1
时间窗: From first dose of study treatment until disease progression, start of new anti-tumor therapy, withdrawal of consent, or death, up to 24 months.
The proportion of patients achieving complete response (CR) or partial response (PR) as assessed by blinded independent central review (BICR) according to RECIST v1.1 criteria. Responses must be confirmed at least 4 weeks after initial documentation.
Objective Response Rate (ORR) in patients with unresectable TP53-mutant advanced HCC
时间窗: From first dose of study treatment until disease progression, start of new anti-tumor therapy, withdrawal of consent, or death, up to 24 months.
Proportion of participants achieving complete response (CR) or partial response (PR) according to RECIST v1.1 criteria, confirmed by imaging at least 4 weeks after the initial response. Assessments include CT or MRI scans performed every 6 weeks (±7 days) during treatment.
次要结局
未报告次要终点
研究者
Zhang Bi Xiang, MD
Professor
Tongji Hospital