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Tyrosine Kinase Inhibitor

Lenvatinib + Pembrolizumab for Liver Cancer

Phase 3
Waitlist Available
Research Sponsored by Merck Sharp & Dohme Corp.
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Has Barcelona Clinic Liver Cancer (BCLC) Stage C disease, or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach
Has a diagnosis of hepatocellular carcinoma confirmed by radiology, histology, or cytology
Must not have
Has significant cardiovascular impairment within 12 months of the first dose of study intervention such as history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular accident stroke, or cardiac arrhythmia associated with hemodynamic instability
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
Timeline
Screening 3 weeks
Treatment Varies
Follow Up up to approximately 41 months
Awards & highlights
Pivotal Trial

Summary

This trial is testing a combination of two drugs, lenvatinib and pembrolizumab, against lenvatinib alone. The study focuses on adults with advanced liver cancer. Lenvatinib works by stopping cancer cells from growing, while pembrolizumab helps the immune system fight the cancer. The goal is to see if this combination improves survival and delays cancer progression better than lenvatinib alone. Lenvatinib combined with pembrolizumab has shown promising results in early phase studies for hepatocellular carcinoma (HCC).

Who is the study for?
Adults over 18 with advanced hepatocellular carcinoma (a type of liver cancer) who haven't had certain treatments like anti-PD-1 or systemic chemotherapy for HCC in the past 3 years. They should be physically capable (ECOG status 0-1), have a life expectancy over 3 months, and not have conditions that could affect study participation or drug absorption.
What is being tested?
The trial is testing if combining lenvatinib, a cancer medication, with pembrolizumab, an immunotherapy drug, is more effective than lenvatinib alone for first-line treatment of liver cancer. The main goal is to see if this combination improves survival without the disease getting worse.
What are the potential side effects?
Possible side effects include high blood pressure, fatigue, diarrhea, decreased appetite and weight loss from lenvatinib; pembrolizumab may cause immune system-related side effects such as inflammation in organs like lungs or intestines.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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My liver cancer is at a stage where it can't be cured with surgery or local treatments.
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My liver cancer diagnosis was confirmed through imaging or lab tests.
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My liver is functioning well.
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I am fully active or restricted in physically strenuous activity but can do light work.
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I have a liver cancer lesion that can be measured.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
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I haven't had major heart problems or strokes in the last year.
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I have had pneumonitis treated with steroids or have it now.
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I have been treated with specific immune therapy for cancer.
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I have been treated for an autoimmune disease in the last 2 years.
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I have a condition that affects how my body absorbs medication.
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I have a severe fistula.
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My heart's pumping ability is below normal.
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I have received an organ or tissue transplant from another person.
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I had major liver surgery less than 4 weeks ago.
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I have active tuberculosis.
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I have had bleeding from varices in my esophagus or stomach in the past 6 months.
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I have an immune system disorder or have been on steroids or other immune-weakening medicines recently.
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I have or had cancer spread to my brain or spinal cord.
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I have not had chemotherapy for liver cancer or any cancer in the last 3 years.
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I have a serious wound or broken bone that is not healing.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~up to approximately 41 months
This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 41 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.
Primary study objectives
Overall Survival (OS)
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Secondary study objectives
Disease Control Rate (DCR) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
Disease Control Rate (DCR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Duration of Response (DOR) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
+11 more

Side effects data

From 2024 Phase 3 trial • 794 Patients • NCT03713593
47%
Diarrhoea
45%
Hypertension
42%
Hypothyroidism
37%
Decreased appetite
34%
Palmar-plantar erythrodysaesthesia syndrome
33%
Proteinuria
32%
Fatigue
30%
Weight decreased
29%
Aspartate aminotransferase increased
26%
Blood bilirubin increased
25%
Platelet count decreased
23%
Alanine aminotransferase increased
23%
Nausea
22%
Arthralgia
21%
Dysphonia
18%
Abdominal pain
18%
Asthenia
17%
Pruritus
17%
Constipation
16%
Gamma-glutamyltransferase increased
16%
Rash
16%
Oedema peripheral
15%
Hypoalbuminaemia
14%
Lipase increased
14%
Back pain
13%
Cough
13%
Vomiting
12%
Headache
12%
Blood alkaline phosphatase increased
12%
Anaemia
11%
Abdominal pain upper
11%
Pyrexia
11%
Hyponatraemia
11%
Dyspnoea
10%
Amylase increased
10%
Blood creatinine increased
10%
Stomatitis
9%
Hypokalaemia
9%
Insomnia
9%
Neutrophil count decreased
9%
Urinary tract infection
8%
Hyperthyroidism
8%
Dyspepsia
7%
Abdominal distension
7%
White blood cell count decreased
7%
Haematuria
7%
Ascites
6%
Hypertriglyceridaemia
6%
Myalgia
6%
Dizziness
6%
Toothache
6%
Mucosal inflammation
6%
Hyperglycaemia
6%
Hypomagnesaemia
6%
Epistaxis
5%
Hypophosphataemia
5%
Pain in extremity
5%
Dysgeusia
5%
Oropharyngeal pain
5%
Hepatic encephalopathy
5%
Neutropenia
5%
Dry mouth
5%
Malaise
3%
Hyperkalaemia
2%
Pneumonia
2%
General physical health deterioration
1%
Hepatic pain
1%
Pancreatitis
1%
Pneumonia klebsiella
1%
Septic shock
1%
Hepatic failure
1%
Tumour haemorrhage
1%
Angina pectoris
1%
Myocardial infarction
1%
Gastric ulcer haemorrhage
1%
Gastrointestinal haemorrhage
1%
Hepatorenal syndrome
1%
COVID-19
1%
COVID-19 pneumonia
1%
Atrial fibrillation
1%
Immune thrombocytopenia
1%
Acute myocardial infarction
1%
Adrenal insufficiency
1%
Hypophysitis
1%
Colitis
1%
Gastric haemorrhage
1%
Haemorrhoidal haemorrhage
1%
Death
1%
Multiple organ dysfunction syndrome
1%
Immune-mediated hepatitis
1%
Sepsis
1%
Dehydration
1%
Diabetic ketoacidosis
1%
Hypoglycaemia
1%
Tumour lysis syndrome
1%
Cerebrovascular accident
1%
Depressed level of consciousness
1%
Ischaemic stroke
1%
Seizure
1%
Acute kidney injury
1%
Pemphigoid
100%
80%
60%
40%
20%
0%
Study treatment Arm
Lenvatinib + Placebo
Lenvatinib + Pembrolizumab

Awards & Highlights

Pivotal Trial
The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups
Experimental Treatment
Active Control
Group I: lenvatinib plus pembrolizumabExperimental Treatment2 Interventions
Participants receive lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight \<60 kg) orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab will be administered for up to 35 cycles (approximately 24 months). Lenvatinib will be administered until progressive disease or unacceptable toxicity.
Group II: lenvatinib plus placeboActive Control2 Interventions
Participants receive lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight \<60 kg) orally QD plus saline placebo by IV infusion on Day 1 Q3W. Saline placebo will be administered for up to 35 cycles (approximately 24 months). Lenvatinib will be administered until progressive disease or unacceptable toxicity.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
lenvatinib
2018
Completed Phase 3
~1950
pembrolizumab
2017
Completed Phase 3
~5890

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.
Mechanism Of Action
Side Effect Profile
Prior Approvals
Other Research
The most common treatments for Hepatocellular Carcinoma (HCC) include Tyrosine Kinase Inhibitors (TKIs) and Immune Checkpoint Inhibitors (ICIs). TKIs, such as Lenvatinib, work by blocking specific enzymes (tyrosine kinases) involved in the signaling pathways that promote tumor growth and angiogenesis (formation of new blood vessels that supply the tumor). This inhibition can slow down or stop the progression of the cancer. On the other hand, ICIs like Pembrolizumab target immune checkpoints (e.g., PD-1/PD-L1) that cancer cells use to evade the immune system. By blocking these checkpoints, ICIs enhance the body's immune response against cancer cells. The combination of these therapies is particularly significant for HCC patients as it addresses both tumor growth and immune evasion, potentially leading to improved outcomes compared to monotherapy.
Challenges of combination therapy with immune checkpoint inhibitors for hepatocellular carcinoma.

Find a Location

Who is running the clinical trial?

Merck Sharp & Dohme Corp.Lead Sponsor
2,286 Previous Clinical Trials
4,581,694 Total Patients Enrolled
6 Trials studying Hepatocellular Carcinoma
2,701 Patients Enrolled for Hepatocellular Carcinoma
Merck Sharp & Dohme LLCLead Sponsor
4,023 Previous Clinical Trials
5,187,591 Total Patients Enrolled
23 Trials studying Hepatocellular Carcinoma
4,184 Patients Enrolled for Hepatocellular Carcinoma
Eisai Inc.Industry Sponsor
521 Previous Clinical Trials
159,004 Total Patients Enrolled
5 Trials studying Hepatocellular Carcinoma
362 Patients Enrolled for Hepatocellular Carcinoma

Media Library

Lenvatinib (Tyrosine Kinase Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT03713593 — Phase 3
Hepatocellular Carcinoma Research Study Groups: lenvatinib plus pembrolizumab, lenvatinib plus placebo
Hepatocellular Carcinoma Clinical Trial 2023: Lenvatinib Highlights & Side Effects. Trial Name: NCT03713593 — Phase 3
Lenvatinib (Tyrosine Kinase Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT03713593 — Phase 3
~115 spots leftby Dec 2025