A Randomized, Open-Label Phase II Trial of Lenvatinib Plus Tislelizumab With or Without Gefitinib as First-Line Treatment for Unresectable or Advanced Hepatocellular Carcinoma (LENTIG-HCC Study)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 120
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events
研究概览
简要总结
This study is for people with unresectable or advanced hepatocellular carcinoma who have not received previous systemic treatment for liver cancer.
The study will compare lenvatinib plus tislelizumab with or without gefitinib. Participants will be randomly assigned to receive either lenvatinib, tislelizumab, and gefitinib, or lenvatinib and tislelizumab. The study is open-label, so participants and study doctors will know the treatment group.
The main outcomes are progression-free survival and the number of participants with adverse events of special interest. Progression-free survival is the time from randomization until the cancer gets worse or the participant dies. Adverse events of special interest are predefined side effects that require close monitoring.
The study will also evaluate tumor response, overall survival, other side effects, and exploratory biomarkers.
详细描述
This is a prospective, randomized, open-label, phase II clinical trial evaluating lenvatinib plus tislelizumab with or without gefitinib as first-line treatment for unresectable or advanced hepatocellular carcinoma.
Eligible participants will be adults with unresectable or advanced hepatocellular carcinoma who have not received prior systemic anticancer therapy for hepatocellular carcinoma. Participants will be randomly assigned in a 1:1 ratio to receive either lenvatinib plus tislelizumab and gefitinib, or lenvatinib plus tislelizumab. Randomization will be performed centrally. Because gefitinib is administered only in the experimental arm and treatment management differs between groups, the study will be open-label. To reduce assessment bias, radiographic tumor assessments will be evaluated by a blinded independent imaging review committee.
The primary outcome measures are progression-free survival and the number of participants with adverse events of special interest. Progression-free survival will be assessed according to RECIST version 1.1. Adverse events of special interest include protocol-defined events requiring close monitoring, such as selected immune-related, hepatic, gastrointestinal, pulmonary, bleeding, thrombotic, dermatologic, renal, endocrine, and infusion-related events.
Secondary outcomes include overall survival, objective response rate, disease control rate, duration of response, treatment-emergent adverse events, serious adverse events, alpha-fetoprotein response, and conversion to curative-intent local therapy when applicable.
Study treatment will continue until radiographic disease progression, unacceptable toxicity, withdrawal of consent, initiation of new anticancer therapy, death, or other protocol-defined discontinuation criteria. Tumor assessments will be performed at protocol-defined intervals using CT or MRI. Safety will be monitored through adverse event reporting and protocol-defined clinical and laboratory assessments.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Age 18 to 75 years, male or female.
- •Histologically or clinically/radiologically confirmed hepatocellular carcinoma.
- •Unresectable or advanced hepatocellular carcinoma requiring systemic therapy.
- •No prior systemic anticancer therapy for hepatocellular carcinoma.
- •At least one measurable lesion according to RECIST version 1.
- •Eastern Cooperative Oncology Group performance status of 0 to
- •Child-Pugh class A liver function.
- •Life expectancy of at least 12 weeks.
- •Adequate hematologic, hepatic, renal, and coagulation function as defined in the protocol.
- •For participants with hepatitis B virus infection, antiviral therapy must be given according to local practice, and hepatitis B virus DNA must meet protocol-defined requirements.
- •Participants of childbearing potential must agree to use effective contraception during the study and for the protocol-defined period after the last dose of study treatment.
- •Ability to understand and willingness to sign written informed consent.
排除标准
- •Prior systemic anticancer therapy for hepatocellular carcinoma.
- •Known fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, mixed hepatocellular-cholangiocarcinoma, or other non-hepatocellular carcinoma histology.
- •Prior treatment with an epidermal growth factor receptor inhibitor.
- •Uncontrolled hypertension, clinically significant cardiovascular disease, or serious bleeding or thrombotic events within the protocol-defined period.
- •Active or high-risk gastrointestinal bleeding, untreated or inadequately treated esophageal or gastric varices, or clinically significant coagulation disorder.
- •History of interstitial lung disease, drug-induced pneumonitis, radiation pneumonitis requiring steroid treatment, or active pneumonitis.
- •Active autoimmune disease or history of autoimmune disease requiring systemic treatment, except as allowed by the protocol.
- •Active uncontrolled infection, including uncontrolled hepatitis B virus infection or hepatitis C virus infection requiring treatment but not adequately controlled.
- •Known human immunodeficiency virus infection with uncontrolled disease, if applicable according to local regulations.
- •Clinically significant ascites, hepatic encephalopathy, or other evidence of hepatic decompensation.
- •Untreated or symptomatic central nervous system metastases.
- •Major surgery, locoregional therapy, radiotherapy, or other anticancer therapy within the protocol-defined washout period before randomization.
- •Inability to swallow oral medication or any condition that may significantly affect absorption of oral study drugs.
- •Known allergy or hypersensitivity to lenvatinib, tislelizumab, gefitinib, or any of their excipients.
- •Pregnancy or breastfeeding.
- •Any other condition that, in the investigator's judgment, would make the participant unsuitable for the study or interfere with study treatment, safety evaluation, or protocol compliance.
研究组 & 干预措施
Control group：Lenvatinib + Tislelizumab
Lenvatinib + Tislelizumab：Participants in this arm will receive lenvatinib plus tislelizumab as first-line treatment for unresectable or advanced hepatocellular carcinoma. Lenvatinib will be given orally once daily according to body weight. Tislelizumab will be given by intravenous infusion every 3 weeks. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, start of new anticancer therapy, death, or other protocol-defined discontinuation criteria.
干预措施: Lenvatinib (Drug)
Control group：Lenvatinib + Tislelizumab
Lenvatinib + Tislelizumab：Participants in this arm will receive lenvatinib plus tislelizumab as first-line treatment for unresectable or advanced hepatocellular carcinoma. Lenvatinib will be given orally once daily according to body weight. Tislelizumab will be given by intravenous infusion every 3 weeks. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, start of new anticancer therapy, death, or other protocol-defined discontinuation criteria.
干预措施: Tislelizumab (Drug)
Experimental group：Lenvatinib+Tislelizumab+Gefitinib
Lenvatinib+Tislelizumab+Gefitinib： Participants in this arm will receive lenvatinib plus tislelizumab and gefitinib as first-line treatment for unresectable or advanced hepatocellular carcinoma. Lenvatinib will be given orally once daily according to body weight. Tislelizumab will be given by intravenous infusion every 3 weeks. Gefitinib will be given orally at 250 mg once daily. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, start of new anticancer therapy, death, or other protocol-defined discontinuation criteria.
干预措施: Tislelizumab (Drug)
Experimental group：Lenvatinib+Tislelizumab+Gefitinib
Lenvatinib+Tislelizumab+Gefitinib： Participants in this arm will receive lenvatinib plus tislelizumab and gefitinib as first-line treatment for unresectable or advanced hepatocellular carcinoma. Lenvatinib will be given orally once daily according to body weight. Tislelizumab will be given by intravenous infusion every 3 weeks. Gefitinib will be given orally at 250 mg once daily. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, start of new anticancer therapy, death, or other protocol-defined discontinuation criteria.
干预措施: Lenvatinib (Drug)
Experimental group：Lenvatinib+Tislelizumab+Gefitinib
Lenvatinib+Tislelizumab+Gefitinib： Participants in this arm will receive lenvatinib plus tislelizumab and gefitinib as first-line treatment for unresectable or advanced hepatocellular carcinoma. Lenvatinib will be given orally once daily according to body weight. Tislelizumab will be given by intravenous infusion every 3 weeks. Gefitinib will be given orally at 250 mg once daily. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, start of new anticancer therapy, death, or other protocol-defined discontinuation criteria.
干预措施: Gefitinib (Drug)
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events
时间窗: From the first dose of study treatment through 90 days after the last dose of study treatment
Treatment-emergent adverse events are defined as adverse events that occur or worsen after the start of study treatment. Adverse events will be coded and graded according to NCI CTCAE version 5.0. This outcome measure will report the number of participants who experience at least one treatment-emergent adverse event during the study.
Progression-Free Survival
时间窗: From randomization until disease progression or death from any cause, assessed up to 36 months
Progression-free survival is defined as the time from randomization to the first documented radiographic disease progression or death from any cause, whichever occurs first. Disease progression will be assessed by a blinded independent imaging review committee according to RECIST version 1.1.
次要结局
- Overall Survival(From randomization until death from any cause, assessed up to 36 months)
- Objective Response Rate(From randomization until disease progression, start of new anticancer therapy, or study completion, assessed up to 24 months)
- Disease Control Rate(From randomization until disease progression, start of new anticancer therapy, or study completion, assessed up to 24 months)
- Duration of Response(From first documented objective response until disease progression or death from any cause, assessed up to 24 months)