Lenvatinib Plus Tislelizumab With or Without Gefitinib for Advanced Liver Cancer

NCT07829926 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: LENTIG-HCC
• Study Type: interventional
• Target: 120
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Hepatocellular Carcinoma (HCC)

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  From randomization until disease progression or death from any cause, assessed up to 36 months

Secondary Outcomes (4)

• 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

Study Arms (2)

Control group：Lenvatinib + Tislelizumab

ACTIVE COMPARATOR

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

Experimental group：Lenvatinib+Tislelizumab+Gefitinib

EXPERIMENTAL

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

Interventions

Lenvatinib DRUG

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

Control group：Lenvatinib + Tislelizumab; Experimental group：Lenvatinib+Tislelizumab+Gefitinib

Tislelizumab DRUG

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

Control group：Lenvatinib + Tislelizumab; Experimental group：Lenvatinib+Tislelizumab+Gefitinib

Gefitinib DRUG

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

Experimental group：Lenvatinib+Tislelizumab+Gefitinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 1.1.
• Eastern Cooperative Oncology Group performance status of 0 to 1.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• First Affiliated Hospital of Wenzhou Medical University: lead

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

lenvatinib; tislelizumab; Gefitinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2026
• First Posted: September 21, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2028
• Last Updated: September 21, 2026

Record last verified: 2026-09