Pembro + Lenvatinib as First-line Intervention for Advanced Melanoma
Research type
Research Study
Full title
A Phase 3 Randomized, Placebo-controlled Trial to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) and Lenvatinib (E7080/MK-7902) Versus Pembrolizumab Alone as First-line Intervention in Participants with Advanced Melanoma (LEAP-003)
IRAS ID
256361
Contact name
Mark Harries
Contact email
Sponsor organisation
Merck Sharp & Dohme LLC
Eudract number
2018-002520-16
Duration of Study in the UK
5 years, 2 months, 0 days
Research summary
Summary of Research
Melanoma is the most serious form of skin cancer and affects adults of all ages. The 5-year prevalence of melanoma in the European Union is approximately 326,000 patients with an incidence of approximately 83,000 per year and approximately 16,000 deaths annually.
Programmed cell death 1 (PD1) is a protein present on the surface of immune (attacking) cells which fight cancer. When immune cells meet cancer cells, PD1 becomes activated by programmed cell death ligands 1 and 2 (PDL1 and PDL2) which are proteins on the surface of cancer cells. The activated immune cells become exhausted or die thus stopping them from attacking the cancer. The study drug pembrolizumab has been developed to block PD1/PDL1 interaction, thereby increasing the immune attack on cancers.
Pembrolizumab is approved by the Food and Drug Administration and the European Commission for the treatment of both first-line and previously treated patients with advanced melanoma. However, there is a large population (~60%) of patients who do not respond to therapy with anti-PD-1 agents. As such, combination strategies as first-line treatment are needed.
Lenvatinib works by blocking proteins called Vascular Endothelial Growth Factors which cancer cells can use to help themselves grow and develop new blood vessels. Early studies have shown promising efficacy with the combination of lenvatinib and pembrolizumab in participants with melanoma.
This phase 3 study will last approximately 61 months and will recruit approximately 660 participants aged 18+ with advanced melanoma. The purpose of the study is to evaluate the effectiveness and safety of pembrolizumab in combination with lenvatinib, versus pembrolizumab with placebo. Participants will be assigned randomly in 1:1 ratio to one of the two treatment arms.
The study is sponsored by Merck Sharp & Dohme Limited (MSD), and co-funded by MSD and Eisai. It will take place at 4 study centres in UK.
Summary of Results
Summary of Clinical Study Results
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About this summary
This summary describes the main results from one clinical study. The sponsor of this study created this summary to help the people who took part in the study understand the results. If you took part in this study and have questions about it or the study results, please speak with the study staff.
This study summary:
• Does not replace your healthcare professional’s advice. You should always talk to a healthcare professional about any treatment decisions • Is not a recommendation of how to use the study medicine • Does not give advice on how to prescribe the study medicine • Does not mean that the study medicine, or the way it was used in the study, is proven to be safe or to work • May be different than information from other studies • Does not reflect all information about the study medicine Other studies may look at different questions or have different results. Researchers often look at results from many studies to learn how a study medicine can be used safely and if it works for a specific use.
This study may include treatment plans, medicines, or ways to use medicines that have not been approved by your government health authority. If a government health authority approves the study medicine, or a new use of the study medicine, information from this study may or may not be included in the medicine’s approved labeling. You can ask your healthcare professional, your country’s health authority, or your country’s MSD office for any approved labeling for this medicine in your country.
Thank you!
Thank you to those who took part in this clinical study and their families and caregivers. You helped researchers learn more about lenvatinib with pembrolizumab.
Copyright © 2025 Merck & Co., Inc., Rahway, NJ, USA and its affiliates. All rights reserved.
On this page, the phrase “study medicine” refers to drugs, vaccines, other treatments, or preventions used in the study. 08Y3JS Summary of Clinical Study Results
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A clinical study of lenvatinib with pembrolizumab in people with melanoma (MK-7902-003) What is a clinical study?
A clinical study is a type of research designed to learn more about how the body responds to medicines, vaccines, or other treatments.
Researchers look at the results of many clinical studies to understand which treatments work and how they work. It takes lots of people in many clinical studies all around the world to advance medical science. This summary only shows the results from this one clinical study. Other clinical studies may show different results.
Why was this clinical study done?
Researchers did this study to learn if giving a study medicine called lenvatinib with pembrolizumab can treat advanced melanoma.
The bold terms are defined in the box below.
The main goals of this study were to learn:
• If people who received lenvatinib with pembrolizumab lived longer without the cancer growing or spreading than those who received placebo with pembrolizumab • If people who received lenvatinib with pembrolizumab lived longer overall than those who received placebo with pembrolizumab What is a placebo?
A placebo looks like the study medicine, but has no study medicine in it. Using a placebo helps researchers better understand the effects of the study medicine.
• Melanoma is a type of skin cancer
• Advanced means the cancer has spread to other parts of the body and cannot be removed with surgery • Pembrolizumab is a treatment for advanced melanoma that is an immunotherapy, which is a treatment that helps the immune system fight cancer • Lenvatinib, the study medicine, is a targeted therapy, which is a treatment that works to control how specific types of cancer cells grow 08Y3JS Summary of Clinical Study Results
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What kind of clinical study was this?
This was a randomized, double-blind, phase 3 clinical study. These terms are defined in the box below.
This study started in March 2019 and ended in November 2024.
When did this clinical study start and end?
• Randomized: Researchers assigned people by chance to a treatment group • Double-blind: Neither the people in the study nor the researchers knew which study treatment a person took • Phase 3 study: When a study treatment is tested in a large number of people 08Y3JS Summary of Clinical Study Results
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Who took part in this clinical study?
People could take part in the study if they were at least 18 years old and met certain criteria, including if they:
• Had melanoma that could not be removed by surgery • Did not have other certain medical problems The clinical study took place at sites in 18 countries. The table below shows the number of people who took part in each country.
Country
Number of people
Country
Number of people
Australia
16
Italy
78
Austria
2
Poland
17
Brazil
35
Republic of Korea
35
Canada
4
South Africa
17
Chile
101
Spain
113
China
62
Sweden
16
France
65
Switzerland
7
Germany
32
United Kingdom
13
Israel
39
United States
22
Total 674 people
About the people in this study:
674 people with advanced melanoma
410 males and 264 females
Average age: 62 years old
Age range: 19 to 89 years old
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What happened during this clinical study?
People received 1 of 2 treatments in this study:
• Lenvatinib with pembrolizumab
• Placebo with pembrolizumab
How treatment was given: by mouth as a capsule How often: once a day How treatment was given: by mouth as a capsule How often: once a day How treatment was given: into a vein as an intravenous (IV) infusion How often: once every 3 weeks People provided a tumor tissue sample to researchers.
Researchers assigned people by equal chance to one of these treatment groups:
Group 1 (334 people)
Group 2 (340 people)
People received lenvatinib with pembrolizumab People received placebo with pembrolizumab During the study, people:
• Had urine, blood, tumor, and imaging tests • Had physical examinations • Had tests to check their heart • Answered questions about how they were feeling and their ability to carry out daily tasks
670 people received at least 1 dose of study treatment. People may have received treatment until:
• The cancer got worse
• They could not tolerate the treatment
• They received the number of treatments allowed, or • They left the study Treatment studied During study treatment Before study treatment 08Y3JS Summary of Clinical Study Results
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After treatment, researchers continued to check:
• If a person had a health problem for up to about 4 months • The size of tumors or if there were any new tumors every 3 months • If people were alive Overall results of this clinical study How long did people live without the cancer growing or spreading?
Researchers learned that people who received lenvatinib with pembrolizumab lived longer without the cancer growing or spreading than people who received placebo with pembrolizumab.
To learn this, researchers measured progression-free survival (PFS) for all people in the study, including people who were assigned to receive study treatment but did not receive treatment.
PFS was the length of time people lived after they started the study until the cancer grew or spread. Median PFS was the length of time after starting the study at which half the people lived without the cancer growing or spreading, and half the people had the cancer grow or spread.
The median PFS was:
• 9.1 months for the 334 people in Group 1 (lenvatinib with pembrolizumab) • 4.2 months for the 340 people in Group 2 (placebo with pembrolizumab) How long did people live overall after treatment?
Researchers learned that people who received lenvatinib with pembrolizumab did not live longer overall than people who received placebo with pembrolizumab.
To learn this, researchers measured the overall survival (OS) for all people in the study, including people who were assigned to receive study treatment but did not receive study treatment.
OS was the length of time that people were alive from the start of the study. Median OS was the length of time after starting the study at which half the people were alive and half the people had died.
The median OS was:
• 25.8 months for the 334 people in Group 1 (lenvatinib with pembrolizumab) • 39.5 months for the 340 people in Group 2 (placebo with pembrolizumab) After study treatment 08Y3JS Summary of Clinical Study Results
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What adverse reactions did people have during this clinical study?
Researchers looked at any adverse reactions and serious adverse reactions a person had during this study. These terms are defined in the box below.
This summary only provides information on the adverse reactions recorded during this study. Other studies may record different adverse reactions.
What serious adverse reactions were reported?
Of the 670 people who were treated during the study:
• 97 people (14.5%) had a serious adverse reaction • 50 people (7.5%) stopped study treatment because of a serious adverse reaction • 5 people (0.7%) died during the study because of a serious adverse reaction Adverse reactions are health problems that the researchers believe could be related to the treatment a person received in a study.
Adverse reaction
Researchers consider an adverse reaction to be serious when it:
•Causes lasting problems
•Requires hospital care
Serious adverse reaction
•Is life-threatening
•Results in death 08Y3JS
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The table below shows the serious adverse reactions that happened in 1% (1 of 100) or more people in any group.
Serious
adverse reaction
Number (%) of people
Group 1:
Lenvatinib with pembrolizumab (out of 332 people) Group 2:
Placebo with pembrolizumab (out of 338 people) Frequent, loose, or watery stools
5 (1.5%)
3 (0.9%)
Swelling of the liver caused by the body’s immune system attacking its own tissues
3 (0.9%)
2 (0.6 %)
An illness that causes the body to not make enough cortisol (a hormone)
3 (0.9%)
1 (0.3%)
A blood clot that blocks blood flow in the lungs
4 (1.2%)
0 (0%)
Sudden heart attack
3 (0.9%)
0 (0%)
Swelling of the colon (large intestine)
3 (0.9%)
0 (0%)
High blood pressure
3 (0.9%)
0 (0%)
Swelling of the pancreas (an organ in the upper stomach area)
3 (0.9%)
0 (0%)
Fever
3 (0.9%)
0 (0%) 08Y3JS
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What were the most common non-serious adverse reactions reported?
Researchers also recorded non-serious adverse reactions that happened during the clinical study.
610 out of 670 people (91%) had a non-serious adverse reaction.
The table below shows the most common non-serious adverse reactions that happened in 20% (20 of 100) or more people in any group.
Non-serious
adverse reaction
Number (%) of people
Group 1:
Lenvatinib with pembrolizumab (out of 332 people) Group 2:
Placebo with pembrolizumab (out of 338 people) High blood pressure
182 (54.8%)
58 (17.2%)
Low level of thyroid hormone in the blood
152 (45.8%)
43 (12.7%)
Frequent, loose, or watery stools
137 (41.3%)
54 (16%)
Feeling tired and weak
75 (22.6%)
66 (19.5%)
Lack of energy and strength
81 (24.4%)
58 (17.2%)
Itching
56 (16.9%)
70 (20.7%)
Increased level of protein in the urine
92 (27.7%)
32 (9.5%)
High level of a protein called lipase that helps the body break down fat
73 (22%)
49 (14.5%)
Feeling sick to one’s stomach
78 (23.5%)
40 (11.8%)
Less hungry than usual
85 (25.6%)
29 (8.6%) 08Y3JS
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How has this clinical study helped researchers?
The results from this study may help researchers learn more about lenvatinib with pembrolizumab.
Are there plans for future clinical studies?
Researchers may continue to do clinical studies to learn more about lenvatinib with pembrolizumab.
Where can I find more information about this clinical study?
To learn more about this clinical study, visit:
• ClinicalTrials.gov at Study Record | ClinicalTrials.gov • European Union clinical register at Clinical Trials register - MK-7902-003 08Y3JS Summary of Clinical Study Results
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For questions about this summary, contact the clinical study sponsor, Merck Sharp & Dohme LLC (Rahway, NJ, USA), at: ClinicalTrialsDisclosure@msd.com Full study title: A Phase 3 Randomized, Placebo-controlled Trial to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) and Lenvatinib (E7080/MK-7902) Versus Pembrolizumab Alone as First-line Intervention in Participants with Advanced Melanoma (LEAP-003) Sponsor of this clinical study: Merck Sharp & Dohme LLC (Rahway, NJ, USA) a subsidiary of Merck & Co., Inc.
Protocol number: MK-7902-003
Clinical trial identifiers:
• EU CT number: Not applicable
• EudraCT number: 2018-002520-16
• US NCT number: NCT03820986
Date: 12-Sept-2025
Thank you!
Thank you to those who took part in this clinical study and to their families and caregivers. You helped researchers learn more about lenvatinib with pembrolizumab.
08Y3JSREC name
East of England - Cambridgeshire and Hertfordshire Research Ethics Committee
REC reference
18/EE/0404
Date of REC Opinion
11 Feb 2019
REC opinion
Further Information Favourable Opinion