NCT07412054

Lenvatinib and Pembrolizumab With or Without BCAA in Unresectable HCC

A Multicenter, Open-Label, Randomized, Phase II Study of Lenvatinib Plus Pembrolizumab With or Without Branched-Chain Amino Acids in Unresectable Hepatocellular Carcinoma

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 234 (estimated)
• Sponsor: Fudan University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to learn whether adding branched-chain amino acids (BCAAs) to lenvatinib and pembrolizumab improves treatment outcomes in adults with unresectable hepatocellular carcinoma (HCC). The study will also evaluate the safety of this combination treatment. The main questions this study aims to answer are: Does the addition of BCAAs improve the time patients live without their cancer getting worse? Does the combination treatment improve tumor response compared with standard treatment alone? What medical problems or side effects do participants experience during treatment? Researchers will compare lenvatinib plus pembrolizumab with BCAAs to lenvatinib plus pembrolizumab alone to see whether adding BCAAs provides additional benefit for patients with unresectable HCC. Participants will: Be randomly assigned to receive lenvatinib and pembrolizumab with or without oral BCAAs Take lenvatinib by mouth every day and receive pembrolizumab by intravenous infusion every 3 weeks Continue treatment until disease progression, unacceptable side effects, or withdrawal from the study Visit the clinic regularly for physical examinations, imaging tests, blood tests, and safety assessments

Detailed description

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, and most patients are diagnosed at an advanced or unresectable stage. Combination therapy with antiangiogenic agents and immune checkpoint inhibitors, such as lenvatinib plus pembrolizumab, has demonstrated promising antitumor activity; however, clinical outcomes remain heterogeneous, and strategies to further improve efficacy are needed. Branched-chain amino acids (BCAAs) are essential amino acids that play an important role in nutritional status, liver function, and immune regulation in patients with chronic liver disease and HCC. Previous clinical and translational studies suggest that BCAA supplementation may improve nutritional balance, liver reserve, and treatment tolerance, and may potentially enhance antitumor immune responses. However, the clinical benefit of adding BCAAs to combination systemic therapy in unresectable HCC has not been prospectively evaluated. This multicenter, open-label, randomized phase II study is designed to evaluate the efficacy and safety of lenvatinib plus pembrolizumab with or without BCAA supplementation in adult patients with unresectable hepatocellular carcinoma. Eligible participants will be randomized to receive standard combination therapy with lenvatinib and pembrolizumab, either with the addition of oral BCAAs or without BCAAs, according to the assigned treatment group. Study treatment will continue until radiographic disease progression, unacceptable toxicity, withdrawal of consent, or completion of the planned treatment period. Efficacy assessments will be performed using standardized radiologic evaluations at predefined intervals. Safety will be monitored throughout the study by the assessment of adverse events, laboratory tests, and clinical examinations. In addition to clinical efficacy and safety outcomes, exploratory analyses will be conducted to investigate potential biomarkers associated with treatment response and resistance. Tumor tissue and peripheral blood samples may be collected for exploratory translational research, including analyses related to immune response and metabolic status. The results of this study are expected to provide evidence on whether BCAA supplementation can enhance the clinical benefit of lenvatinib plus pembrolizumab while maintaining an acceptable safety profile in patients with unresectable hepatocellular carcinoma, and to inform future clinical development strategies for combination systemic therapy in this population.

Conditions

• HCC - Hepatocellular Carcinoma

Interventions

Type	Name	Description
DRUG	Lenvatinib	Lenvatinib is administered orally once daily at a dose of 12 mg for participants with body weight ≥60 kg or 8 mg for participants with body weight \<60 kg. Treatment is continued in 21-day cycles until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision.
DRUG	Pembrolizumab	Pembrolizumab is administered as an intravenous infusion at a fixed dose of 200 mg on Day 1 of each 21-day treatment cycle. Treatment is continued for up to 2 years or until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision.
DRUG	Branched-Chain Amino Acids	Branched-chain amino acids (BCAA) are administered orally at a dose of 6 g twice daily (po bid). BCAA supplementation is continued throughout the treatment period unless discontinued due to intolerance, withdrawal of consent, or investigator decision.

Timeline

• Start date: 2026-03-01
• Primary completion: 2027-06-01
• Completion: 2028-06-01
• First posted: 2026-02-17
• Last updated: 2026-02-17