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HCC - Hepatocellular CarcinomaPhase 2BLP-HCCNCT07412054

Lenvatinib and Pembrolizumab With or Without BCAA in Unresectable HCC

A Phase 2 study testing Lenvatinib, Pembrolizumab and Branched-Chain Amino Acids in people with HCC - Hepatocellular Carcinoma, run by Fudan University.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
HCC - Hepatocellular Carcinoma
What is being tested?
Lenvatinib, Pembrolizumab and Branched-Chain Amino Acids
Could I receive a placebo?
No, everyone receives an active treatment
How many people
234 participants
Where
No sites listed yet
Study dates
1 Mar 2026to 1 Jun 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
Show all 11Show fewer
  • 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.

Who cannot join

  • 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.
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  • 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.
  • History or presence of significant bleeding tendency, including but not limited to:
  • Major gastrointestinal bleeding within 6 months prior to enrollment;
  • Untreated high-risk esophageal or gastric varices;
  • Severe coagulation abnormalities (e.g., INR >2.0, unless due to stable anticoagulation therapy).
  • Concurrent participation in another clinical trial, unless it is an observational, non-interventional study or the follow-up phase of an interventional study.
  • History of hepatic encephalopathy, refractory ascites, or severe portal hypertension syndrome caused by hepatic vein or portal vein thrombosis, deemed unsuitable for study treatment by the investigator.
  • Known history of severe hypersensitivity reactions to lenvatinib, pembrolizumab, branched-chain amino acid preparations, or any of their excipients.
  • Expected survival of less than 3 months.
  • Participation in another interventional clinical trial within 4 weeks prior to enrollment (during the treatment phase), or currently receiving treatment in another interventional study; participants who have entered the follow-up phase of another clinical trial and do not interfere with the assessment of this study may be enrolled.
  • Any other condition that, in the investigator's judgment, may compromise participant safety or interfere with the evaluation of study efficacy.

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Jinhong Chen, M.D contact

+8613801977742

Jinhongch@hotmail.com

Chenhe Yi, M.D contact

+8618817365173

chenheyi@fudan.edu.cn

About this study

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

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:

Read more

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

Read the 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.

Being tested
Lenvatinib, Pembrolizumab, Branched-Chain Amino Acids
Keywords
Hepatocellular carcinoma, Branched-chain amino acids, Lenvatinib, Pembrolizumab, Randomized controlled trial
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LenvatinibDrug

    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.

  • PembrolizumabDrug

    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.

  • Branched-Chain Amino AcidsDrug

    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.

Study groups in NCT07412054
Study groupRoleWhat they receive
Lenvatinib + Pembrolizumab + BCAAExperimentalParticipants 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.
Receives: Drug: Lenvatinib; Drug: Pembrolizumab; Drug: Branched-Chain Amino Acids
Lenvatinib + PembrolizumabActive comparatorParticipants 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.
Receives: Drug: Lenvatinib; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (4)

  1. Overall Survival (OS)

    Overall survival (OS), defined as the time from randomization to death from any cause.

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

  2. Objective Response Rate (ORR)

    Objective response rate (ORR), defined as the proportion of participants achieving complete response (CR) or partial response (PR) according to RECIST version 1.1.

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

  3. Disease Control Rate (DCR)

    Disease control rate (DCR), defined as the proportion of participants achieving complete response (CR), partial response (PR), or stable disease (SD) according to RECIST version 1.1.

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

  4. Incidence and Severity of Adverse Events

    Incidence and Severity of Adverse Events

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Feb 2026
  2. Study start1 Mar 2026 (estimated)
  3. Primary completion1 Jun 2027 (estimated)
  4. Study completion1 Jun 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
234 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07412054
Sponsor's protocol ID
BCAA-LP-Ph2-25
Other IDs
KY-2025-1568
Acronym
BLP-HCC
Status last verified
Feb 2026
First submitted
9 Feb 2026
Last updated
17 Feb 2026
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 21874260

  • 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.

    PubMed 15043519

  • 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.

    PubMed 12806613

  • 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.

    PubMed 36753026

  • 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.

    PubMed 38039993

  • 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.

    PubMed 34087115

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lenvatinib, Pembrolizumab and Branched-Chain Amino Acids in people with HCC - Hepatocellular Carcinoma, run by Fudan University.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 17 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Jinhong Chen, M.D (+8613801977742, Jinhongch@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-Free Survival (PFS) (time frame: From randomization until disease progression or death, assessed up to approximately 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07412054, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2026.

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