Lenvatinib and Pembrolizumab With or Without BCAA in Unresectable HCC

NCT07412054 | Not Yet Recruiting Phase 2

• 2 other identifiers: BCAA-LP-Ph2-25KY-2025-1568
• Study Type: interventional
• Target: 234
• Locations: 0 countries
• Sites: N/A

Brief 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

Conditions

HCC - Hepatocellular Carcinoma

Keywords

Hepatocellular carcinoma; Branched-chain amino acids; Lenvatinib; Pembrolizumab; Randomized controlled trial

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  Progression-free survival (PFS), defined as the time from randomization to the first documented disease progression according to RECIST version 1.1 or death from any cause, whichever occurs first.

  From randomization until disease progression or death, assessed up to approximately 24 months

Secondary Outcomes (4)

• Overall Survival (OS)

  From randomization until death from any cause, assessed up to approximately 36 months.

• Objective Response Rate (ORR)

  Assessed from baseline until disease progression, assessed up to approximately 24 months.

• Disease Control Rate (DCR)

  Assessed from baseline until disease progression, assessed up to approximately 24 months.

• Incidence and Severity of Adverse Events

  From first dose of study treatment until 30 days after the last dose.

Other Outcomes (1)

• Exploratory Biomarker Analyses

  From baseline through disease progression or end of study follow-up, assessed up to approximately 36 months.

Study Arms (2)

Lenvatinib + Pembrolizumab + BCAA

EXPERIMENTAL

Participants in this arm will receive oral lenvatinib at a dose of 12 mg once daily for patients with a body weight ≥60 kg or 8 mg once daily for patients with a body weight \<60 kg. Pembrolizumab will be administered at a dose of 200 mg by intravenous infusion on Day 1 of each 21-day treatment cycle, for a maximum duration of up to 2 years after Cycle 1 Day 1. In addition, participants will receive oral branched-chain amino acid (BCAA) supplementation at a dose of 6 g twice daily.

Drug: Lenvatinib; Drug: Pembrolizumab; Drug: Branched-Chain Amino Acids

Lenvatinib + Pembrolizumab

ACTIVE COMPARATOR

Participants in this arm will receive oral lenvatinib at a dose of 12 mg once daily for patients with a body weight ≥60 kg or 8 mg once daily for patients with a body weight \<60 kg. Pembrolizumab will be administered at a dose of 200 mg by intravenous infusion on Day 1 of each 21-day treatment cycle, for a maximum duration of up to 2 years after Cycle 1 Day 1.

Drug: Lenvatinib; Drug: Pembrolizumab

Interventions

Lenvatinib DRUG

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.

Lenvatinib + Pembrolizumab; Lenvatinib + Pembrolizumab + BCAA

Pembrolizumab DRUG

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.

Lenvatinib + Pembrolizumab; Lenvatinib + Pembrolizumab + BCAA

Branched-Chain Amino Acids DRUG

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.

Lenvatinib + Pembrolizumab + BCAA

Eligibility Criteria

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

You may qualify if:

• Adults aged ≥18 years and \<75 years at the time of enrollment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histologically or cytologically confirmed hepatocellular carcinoma (HCC), excluding fibrolamellar carcinoma, sarcomatoid HCC, or mixed hepatocellular-cholangiocarcinoma; or clinically diagnosed HCC according to the American Association for the Study of Liver Diseases (AASLD) criteria.
• Unresectable Barcelona Clinic Liver Cancer (BCLC) stage B or C disease, as assessed by the investigator.
• At least one measurable lesion according to RECIST version 1.1.
• Adequate liver function defined as Child-Pugh class A (score 5-6).
• Adequate hematologic function: absolute neutrophil count ≥1.5 × 10⁹/L, hemoglobin ≥9.0 g/dL, and platelet count ≥100 × 10⁹/L.
• Adequate hepatic and renal function: total bilirubin ≤1.5 × upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 × ULN; serum creatinine ≤1.5 × ULN.
• Adequate coagulation function: international normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤1.5 × ULN.
• Participants of childbearing potential must agree to use effective contraception during the study and for at least 120 days after the last dose of study treatment; female participants of childbearing potential must have a negative urine or serum pregnancy test within 3 days prior to the first dose of study treatment.
• Ability to understand and willingness to sign a written informed consent form.

You may not qualify if:

• Pregnant or breastfeeding women.
• Prior treatment with systemic targeted therapies (including sorafenib or lenvatinib), immune checkpoint inhibitors (including anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies), or any form of cellular immunotherapy.
• Active autoimmune disease requiring systemic treatment within the past 2 years (e.g., disease-modifying agents, corticosteroids, or immunosuppressive drugs); replacement therapies (such as thyroxine, insulin, or physiologic corticosteroid replacement for adrenal or pituitary insufficiency) are not considered systemic treatment.
• Active or uncontrolled infection, including but not limited to uncontrolled acute exacerbation of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, active tuberculosis, human immunodeficiency virus (HIV) infection with significantly reduced CD4 counts, or severe bacterial, fungal, or viral infections requiring intravenous antimicrobial therapy.
• History of another malignancy within 3 years prior to enrollment, except for adequately treated localized malignancies (such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or cervical carcinoma in situ).
• Severe psychological or psychiatric disorders.
• Significant cardiovascular disease or cardiac dysfunction, including but not limited to:
• New York Heart Association (NYHA) class III-IV heart failure;
• Myocardial infarction, severe angina, coronary stent placement, or coronary artery bypass grafting within 6 months prior to enrollment;
• Clinically significant ventricular arrhythmias or persistent atrial fibrillation;
• Uncontrolled hypertension (blood pressure ≥150/90 mmHg despite optimal medical therapy).
• Severe pulmonary disease, including:
• Severe chronic obstructive pulmonary disease (COPD) or interstitial lung disease requiring long-term oxygen therapy;
• Active severe pulmonary infection.
• Severe renal impairment, including acute or chronic renal failure with estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m² or requiring dialysis.

Sponsors & Collaborators

• Fudan University: lead

Related Publications (6)

• Yoshiji H, Noguchi R, Ikenaka Y, Kaji K, Aihara Y, Yamazaki M, Yamao J, Toyohara M, Mitoro A, Sawai M, Yoshida M, Morioka C, Fujimoto M, Uemura M, Fukui H. Combination of branched-chain amino acids and angiotensin-converting enzyme inhibitor suppresses the cumulative recurrence of hepatocellular carcinoma: a randomized control trial. Oncol Rep. 2011 Dec;26(6):1547-53. doi: 10.3892/or.2011.1433. Epub 2011 Aug 24.

  PMID: 21874260 RESULT

• Poon RT, Yu WC, Fan ST, Wong J. Long-term oral branched chain amino acids in patients undergoing chemoembolization for hepatocellular carcinoma: a randomized trial. Aliment Pharmacol Ther. 2004 Apr 1;19(7):779-88. doi: 10.1111/j.1365-2036.2004.01920.x.

  PMID: 15043519 RESULT

• Marchesini G, Bianchi G, Merli M, Amodio P, Panella C, Loguercio C, Rossi Fanelli F, Abbiati R; Italian BCAA Study Group. Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial. Gastroenterology. 2003 Jun;124(7):1792-801. doi: 10.1016/s0016-5085(03)00323-8.

  PMID: 12806613 RESULT

• Yang X, Chen B, Wang Y, Wang Y, Long J, Zhang N, Xue J, Xun Z, Zhang L, Cheng J, Lei J, Sun H, Li Y, Lin J, Xie F, Wang D, Pan J, Hu K, Guan M, Huo L, Shi J, Yu L, Zhou L, Zhou J, Lu Z, Yang X, Mao Y, Sang X, Lu Y, Zhao H. Real-world efficacy and prognostic factors of lenvatinib plus PD-1 inhibitors in 378 unresectable hepatocellular carcinoma patients. Hepatol Int. 2023 Jun;17(3):709-719. doi: 10.1007/s12072-022-10480-y. Epub 2023 Feb 8.

  PMID: 36753026 RESULT

• Llovet JM, Kudo M, Merle P, Meyer T, Qin S, Ikeda M, Xu R, Edeline J, Ryoo BY, Ren Z, Masi G, Kwiatkowski M, Lim HY, Kim JH, Breder V, Kumada H, Cheng AL, Galle PR, Kaneko S, Wang A, Mody K, Dutcus C, Dubrovsky L, Siegel AB, Finn RS; LEAP-002 Investigators. Lenvatinib plus pembrolizumab versus lenvatinib plus placebo for advanced hepatocellular carcinoma (LEAP-002): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2023 Dec;24(12):1399-1410. doi: 10.1016/S1470-2045(23)00469-2.

  PMID: 38039993 RESULT

• Vogel A, Qin S, Kudo M, Su Y, Hudgens S, Yamashita T, Yoon JH, Fartoux L, Simon K, Lopez C, Sung M, Mody K, Ohtsuka T, Tamai T, Bennett L, Meier G, Breder V. Lenvatinib versus sorafenib for first-line treatment of unresectable hepatocellular carcinoma: patient-reported outcomes from a randomised, open-label, non-inferiority, phase 3 trial. Lancet Gastroenterol Hepatol. 2021 Aug;6(8):649-658. doi: 10.1016/S2468-1253(21)00110-2. Epub 2021 Jun 2.

  PMID: 34087115 RESULT

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

lenvatinib; pembrolizumab; Amino Acids, Branched-Chain

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)

Amino Acids; Amino Acids, Peptides, and Proteins

Central Study Contacts

Jinhong Chen, M.D

CONTACT

+8613801977742; Jinhongch@hotmail.com

Chenhe Yi, M.D

CONTACT

+8618817365173; chenheyi@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Department of Hepatobiliary Surgery, Huashan Hospital, Fudan University

Study Record Dates

• First Submitted: February 9, 2026
• First Posted: February 17, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share