A Phase 2 interventional study of Lenvatinib and Tislelizumab in Hepatocellular Carcinoma (HCC), sponsored by First Affiliated Hospital of Wenzhou Medical University. Not yet recruiting. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-09-21.
Sponsored by First Affiliated Hospital of Wenzhou Medical University · Phase 2, Interventional, and Treatment
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.
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.
Exploratory analyses may include evaluation of epidermal growth factor receptor-related biomarkers, tumor immune microenvironment, circulating tumor DNA, tumor mutation profiles, alpha-fetoprotein dynamics, and other candidate biomarkers to explore potential associations with treatment response, disease progression, resistance, and safety.
Exclusion Criteria：
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.
Drug: Lenvatinib · Drug: Tislelizumab
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.
Drug: Lenvatinib · Drug: Tislelizumab · Drug: Gefitinib
Lenvatinib will be administered orally once daily. The dose will be based on baseline body weight: 8 mg once daily for participants weighing less than 60 kg and 12 mg once daily for participants weighing 60 kg or more. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, start of new anticancer therapy, death, or other protocol-defined discontinuation criteria.
Also known as: LEN
Tislelizumab will be administered by intravenous infusion at a dose of 200 mg on Day 1 of each 21-day cycle. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, start of new anticancer therapy, death, or other protocol-defined discontinuation criteria.
Also known as: TIS
Gefitinib will be administered orally at a dose of 250 mg once daily in the experimental arm. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, start of new anticancer therapy, death, or other protocol-defined discontinuation criteria.
Also known as: GEF
Number of Participants With Treatment-Emergent Adverse Events
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.
Time frame: From the first dose of study treatment through 90 days after the last dose of study treatment
Progression-Free Survival
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.
Time frame: From randomization until disease progression or death from any cause, assessed up to 36 months
Overall Survival
Overall survival is defined as the time from randomization to death from any cause.
Time frame: From randomization until death from any cause, assessed up to 36 months
Objective Response Rate
Objective response rate is defined as the proportion of participants with a best overall response of complete response or partial response, as assessed according to RECIST version 1.1.
Time frame: From randomization until disease progression, start of new anticancer therapy, or study completion, assessed up to 24 months
Disease Control Rate
Disease control rate is defined as the proportion of participants with a best overall response of complete response, partial response, or stable disease, as assessed according to RECIST version 1.1.
Time frame: From randomization until disease progression, start of new anticancer therapy, or study completion, assessed up to 24 months
Duration of Response
Duration of response is defined for participants who achieve complete response or partial response as the time from the first documented objective response to the first documented disease progression or death from any cause, whichever occurs first.
Time frame: From first documented objective response until disease progression or death from any cause, assessed up to 24 months
No study locations are listed for this record.
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First Affiliated Hospital of Wenzhou Medical University