AzTrials
AzTrials

Malignant MelanomaPhase 3NCT03820986

Safety and Efficacy Study of Pembrolizumab (MK-3475) Combined With Lenvatinib (MK-7902/E7080) as First-line Intervention in Adults With Advance Melanoma (MK-7902-003/E7080-G000-312/LEAP-003)

A Phase 3 study testing Pembrolizumab and Lenvatinib in people with Malignant Melanoma, run by Merck Sharp & Dohme LLC at 119 sites in 18 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475) combined with lenvatinib (MK-7902/E7080) compared to pembrolizumab alone (with placebo for lenvatinib) as first-line treatment in adults with no prior systemic therapy for their advanced melanoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Melanoma
What is being tested?
Pembrolizumab and Lenvatinib
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
674 participants
Where
119 sitesin 18 countries
Study dates
12 Mar 2019to 1 Nov 2024
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Has histologically or cytologically confirmed melanoma.
  • Has unresectable Stage III or Stage IV melanoma, as per American Joint Committee on Cancer guidelines, not amenable to local therapy.
  • Has been untreated for advanced or metastatic disease except as follows:
  • Proto-oncogene B-Raf (BRAF) V600 mutation-positive melanoma may have received standard of care targeted therapy as first-line therapy for advanced or metastatic disease. Participants that do not have a BRAF V600 mutation but did receive BRAF or BRAF/mitogen-activated extracellular signal-regulated kinase 1/2 Inhibitor (MEKi) therapy are eligible to participate in this study after discussion with the medical monitor.
  • Prior adjuvant or neoadjuvant therapy, with targeted therapy or immunotherapy (such as anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], anti-programmed cell death 1 [anti-PD-1] therapy or interferon) will only be permitted if relapse did not occur during active treatment or within 6 months of treatment discontinuation.
  • Have documentation of BRAF V600-activating mutation status or consent to BRAF V600 mutation testing during the Screening period (participants with BRAF mutation-positive melanoma as well as BRAF wild-type or unknown are eligible).
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  • Has an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
  • Has the presence of ≥1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1.
  • Provides a tumor biopsy. Participants must submit tumor sample during Screening for confirmation of adequacy of tumor tissue at a central pathology laboratory. Participants who do not submit a tumor tissue sample will not be randomized. The tumor biopsy may not be obtained from a lone target lesion. Confirmation of presence of tumor tissue is not required prior to randomization.
  • Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia). If participant received major surgery or radiation therapy of >30 Gray (Gy), they must have recovered from the toxicity and/or complications from the intervention.
  • Male participants must agree to use contraception during the treatment period and for at least 7 days after the last dose of study treatment and refrain from donating sperm during this period. Please note that 7 days after lenvatinib/placebo is stopped, if the participant is on pembrolizumab only, no male contraception measures are needed. Contraception use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.
  • Female participants must not be pregnant, not breastfeeding, and ≥1 of the following conditions applies:
  • Not a woman of childbearing potential (WOCBP). OR
  • A WOCBP who agrees to use study-approved contraception during the treatment period and for at least 120 days after the last dose of study treatment.
  • The participant (or legally acceptable representative) has provided documented informed consent for the study.
  • Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mmHg at screening and no change in antihypertensive medications within 1 week before Cycle 1 Day 1.
  • Has adequate organ function.

Who cannot join

  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study treatment.
  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early stage cancers (carcinoma in situ or Stage 1, non-ulcerated primary melanoma <1 mm in depth with no nodal involvement) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy.
  • Has known active central nervous system metastases and/or carcinomatous meningitis.
  • Has ocular melanoma.
  • Has known hypersensitivity to active substances or any of their excipients including previous clinically significant hypersensitivity reaction to treatment with another monoclonal antibody.
  • Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
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  • Has an active infection requiring systemic therapy.
  • Has known history of human immunodeficiency virus (HIV) infection
  • Has known history of or is positive for hepatitis B virus or hepatitis C virus infection.
  • Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • Has a history of active tuberculosis (Bacillus tuberculosis).
  • Gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib.
  • Has had a major surgery within 3 weeks prior to first dose of study intervention. Note: Adequate wound healing after major surgery must be assessed clinically independent of time elapsed for eligibility.
  • Has a preexisting Grade ≥3 gastrointestinal or non-gastrointestinal fistula.
  • Has radiographic evidence of encasement or invasion of major blood vessel, or of intratumoral cavitation.
  • Has active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study treatment.
  • Has clinically significant cardiovascular disease from 12 months of the first dose of study treatment including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
  • Has urine protein ≥1 g/24-hour. Note: Participants with ≥2+ (≥100 mg/dL) proteinuria on urine dipstick testing (or urinalysis) will undergo 24-hour urine collection for quantitative assessment of proteinuria.
  • Prolongation of QTcF interval to >480 ms. Note: If the QTcF is prolonged to >480 ms in the presence of a pacemaker, contact the Sponsor to determine eligibility.
  • Has left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range, as determined by multigated acquisition scan (MUGA) or echocardiogram.
  • Has received prior therapy in the adjuvant setting. Note: Targeted therapy, anti-CTLA-4, or anti-PD-1 may be allowed.
  • Has received prior systemic treatment for unresectable or metastatic melanoma other than targeted therapy as noted in Inclusion Criteria above
  • Has received prior therapy with a monoclonal antibody, chemotherapy, or an investigational agent or device within 4 weeks or 5 half-lives (whichever is longer) before administration of study treatment or not recovered (≤Grade 1 or at Baseline) from adverse events due to previously administered agents.
  • Exception to this rule would be use of denosumab, which is not excluded. Note: Participants with alopecia and ≤Grade 2 neuropathy are an exception and may enroll.
  • Has received prior radiotherapy within 2 weeks of first dose of study treatment (Cycle 1 Day 1). Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
  • Has received live vaccine within 30 days before the first dose of study treatment.
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
  • Has had an allogeneic tissue/solid organ transplant.
  • Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.

Trial locations and contacts

119 sites in 18 countries.

119 sites in 18 countries

United States17 sites

  • University of Colorado Cancer Center ( Site 0708)

    Aurora, Colorado, 80045

  • St. Vincent Frontier Cancer Center ( Site 0724)

    Billings, Montana, 59102

  • University of North Carolina - Cancer Hospital ( Site 0751)

    Chapel Hill, North Carolina, 27514

  • Inova Schar Cancer Institute ( Site 0739)

    Fairfax, Virginia, 22031-4867

  • Minnesota Oncology Specialist, PA ( Site 0766)

    Fridley, Minnesota, 55432

  • Baptist MD Anderson Cancer Center ( Site 0767)

    Jacksonville, Florida, 32207

  • The Angeles Clinic and Research Institute ( Site 0707)

    Los Angeles, California, 90025

  • Atlantic Health System ( Site 0768)

    Morristown, New Jersey, 07960

  • Yale Cancer Center ( Site 0709)

    New Haven, Connecticut, 06510

  • Mid-Florida Cancer Centers ( Site 0764)

    Orange City, Florida, 32763

  • Valley Hospital ( Site 0749)

    Paramus, New Jersey, 07652

  • AMG Oncology ( Site 0714)

    Park Ridge, Illinois, 60068

  • Illinois Cancer Care, PC ( Site 0765)

    Peoria, Illinois, 61615

  • OHSU Center for Health & Healing ( Site 0731)

    Portland, Oregon, 97239

  • UCSF Helen Diller Family Comprehensive Cancer Center ( Site 0704)

    San Francisco, California, 30322

  • California Pacific Medical Center Research Institute ( Site 0705)

    San Francisco, California, 94115

  • John Wayne Cancer Institute ( Site 0706)

    Santa Monica, California, 90404

Other trials in United States

China11 sites

  • Beijing Cancer Hospital ( Site 0601)

    Beijing, Beijing Municipality, 100036

  • The First Hospital Of Jilin University ( Site 0603)

    Changchun, Jilin, 130021

  • Fujian Provincial Cancer Hospital ( Site 0612)

    Fuzhou, Fujian, 350014

  • Sun Yat-Sen University Cancer Center ( Site 0602)

    Guangzhou, Guangdong, 510000

  • Sir Run Run Shaw Hospital ( Site 0605)

    Hangzhou, Zhejiang, 310018

  • Zhejiang Cancer Hospital ( Site 0608)

    Hangzhou, Zhejiang, 310022

  • Yunnan Cancer Hospital ( Site 0604)

    Kunming, Yunnan, 430030

  • Nanjing Drum Tower Hospital ( Site 0609)

    Nanjing, Jiangsu, 210008

  • Fudan University Shanghai Cancer Center ( Site 0607)

    Shanghai, Shanghai Municipality, 200032

  • Tianjin Medical University Cancer Institute & Hospital ( Site 0606)

    Tianjin, Tianjin Municipality, 300060

  • Henan Cancer Hospital ( Site 0610)

    Zhengzhou, Henan, 450003

Other trials in China

France10 sites

  • Centre Hospitalier Victor Dupouy ( Site 0012)

    Argenteuil, Val-d Oise, 95100

  • Hopital Ambroise Pare Boulogne ( Site 0007)

    Boulogne-Billancourt, Hauts-de-Seine, 92100

  • CHU Dijon Bourgogne ( Site 0010)

    Dijon, Cote-d Or, 21079

  • CHRU Lille - Hopital Claude Huriez ( Site 0004)

    Lille, Nord, 59037

  • Hopital La Timone ( Site 0002)

    Marseille, Bouches-du-Rhone, 13385

  • Hopital ARCHET 2 ( Site 0009)

    Nice, Alpes-Maritimes, 06200

  • CHU de la Miletrie Poitiers ( Site 0011)

    Poitiers, Vienne, 86021

  • CHU de Rouen ( Site 0013)

    Rouen, Seine-Maritime, 76000

  • Institut Claudius Regaud IUCT Oncopole ( Site 0003)

    Toulouse, Haute-Garonne, 31059

  • Institut Gustave Roussy ( Site 0001)

    Villejuif, Val-de-Marne, 94805

Other trials in France

Spain9 sites

  • Complejo Hospitalario Universitario A Coruna. CHUAC ( Site 0182)

    A Coruña, La Coruna, 15006

  • Hospital Clinic i Provincial Barcelona ( Site 0190)

    Barcelona, 08036

  • Hospital Duran i Reinals ICO de Hospitalet ( Site 0187)

    Hospitalet Del Llobregat, Barcelona, 08908

  • Hospital Universitario Insular de Gran Canaria ( Site 0189)

    Las Palmas de Gran Canaria, Las Palmas, 35001

  • Hospital General Universitario Gregorio Maranon ( Site 0191)

    Madrid, 28009

  • Hospital Universitario Ramon y Cajal ( Site 0183)

    Madrid, 28034

  • Hospital Universitario La Paz ( Site 0184)

    Madrid, 28046

  • Hospital Universitario Carlos Haya ( Site 0186)

    Málaga, 29010

  • Hospital Universitario Marques de Valdecilla ( Site 0181)

    Santander, Cantabria, 39008

Other trials in Spain

Germany8 sites

  • Hautkrebszentrum Buxtehude ( Site 0037)

    Buxtehude, Lower Saxony, 21614

  • Universitaetsklinikum Carl Gustav Carus ( Site 0041)

    Dresden, Saxony, 01307

  • Universitaetsklinikum Erlangen ( Site 0044)

    Erlangen, Bavaria, 91054

  • SRH Wald-Klinikum Gera GmbH ( Site 0042)

    Gera, Thuringia, 07548

  • Klinik fur Dermatologie Allergologie und Venerologie ( Site 0035)

    Hannover, Baden-Wurttemberg, 30625

  • Universitaetsklinikum Schleswig-Holstein Campus Kiel ( Site 0033)

    Kiel, Schleswig-Holstein, 24105

  • Universitaetsklinikum Leipzig ( Site 0040)

    Leipzig, Saxony, 04103

  • Universitaetsklinikum Wuerzburg-Department of Dermatology ( Site 0036)

    Würzburg, Bavaria, 97080

Other trials in Germany

Israel8 sites

  • HaEmek Medical Center ( Site 0306)

    Afula, 1834111

  • Soroka Medical Center ( Site 0303)

    Beersheba, 8457108

  • Rambam Medical Center ( Site 0301)

    Haifa, 3109601

  • Hadassah Ein Karem Hebrew University Medical Center ( Site 0305)

    Jerusalem, 9112001

  • Rabin Medical Center ( Site 0302)

    Petah Tikva, 4941492

  • Chaim Sheba Medical Center ( Site 0304)

    Ramat Gan, 5262000

  • Sourasky Medical Center ( Site 0307)

    Tel Aviv, 6423906

  • Shamir Medical Center-Assaf Harofeh ( Site 0308)

    Tsrifin, 70300

Other trials in Israel

Sweden7 sites

  • Sahlgrenska Universitetssjukhuset ( Site 0212)

    Gothenburg, Västra Götaland County, 413 45

  • Laenssjukhuset Ryhov ( Site 0215)

    Jönköping, Jönköping County, 551 85

  • Skanes Universitetssjukhus ( Site 0213)

    Lund, Skåne County, 221 85

  • Karolinska Universitetssjukhuset ( Site 0211)

    Solna, Stockholm County, 171 64

  • Norrlands Universitetssjukhus ( Site 0216)

    Umeå, Västerbotten County, 901 85

  • Akademiska Sjukhuset ( Site 0218)

    Uppsala, Uppsala County, 751 85

  • Centrallasarettet Vaxjo ( Site 0214)

    Vaxjo, Kronoberg County, 351 85

Other trials in Sweden

Australia6 sites

  • Eastern Health ( Site 0457)

    Box Hill, Victoria, 3128

  • Lismore Base Hospital ( Site 0453)

    Lismore, Australian Capital Territory, 2480

  • Fiona Stanley Hospital ( Site 0456)

    Murdoch, Western Australia, 6150

  • Melanoma Institute Australia ( Site 0452)

    North Sydney, New South Wales, 2060

  • Westmead Hospital ( Site 0451)

    Westmead, New South Wales, 2145

  • Princess Alexandra Hospital ( Site 0454)

    Wooloongabba, Queensland, 4102

Other trials in Australia

Italy6 sites

  • ASST Papa Giovanni XXIII ( Site 0062)

    Bergamo, Abruzzo, 24127

  • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0064)

    Milan, 20133

  • Istituto Europeo di Oncologia ( Site 0067)

    Milan, 20141

  • Istituto Nazionale Tumori Fondazione Pascale ( Site 0061)

    Naples, 80131

  • Istituto Oncologico Veneto ( Site 0063)

    Padova, 35128

  • Azienda Ospedaliera Universitaria Senese ( Site 0065)

    Siena, Tuscany, 53100

Other trials in Italy

Brazil5 sites

  • PERSONAL - Oncologia de Precisao e Personalizada ( Site 0399)

    Belo Horizonte, Minas Gerais, 30130-090

  • Hospital de Caridade de Ijui ( Site 0391)

    Ijuí, Rio Grande do Sul, 98700-000

  • Hospital Sao Vicente de Paulo ( Site 0396)

    Passo Fundo, Rio Grande do Sul, 99010-080

  • Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0397)

    Porto Alegre, Rio Grande do Sul, 90610-000

  • Instituto Nacional de Cancer Hospital do Cancer II ( Site 0394)

    Rio de Janeiro, 20220-410

Other trials in Brazil

Canada5 sites

  • BC Cancer-Kelowna - Sindi Ahluwalia Hawkins Centre ( Site 0661)

    Kelowna, British Columbia, V1Y 5L3

  • Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0652)

    Montreal, Quebec, H2W 3E4

  • McGill University Health Centre ( Site 0651)

    Montreal, Quebec, H4A 3J1

  • Lions Gate Hospital ( Site 0662)

    North Vancouver, British Columbia, V7L 2L7

  • Sunnybrook Research Institute ( Site 0654)

    Toronto, Ontario, M4N 3M5

Other trials in Canada

Chile5 sites

  • Fundacion Arturo Lopez Perez FALP ( Site 0421)

    Santiago, Region M. de Santiago, 7500921

  • Pontificia Universidad Catolica de Chile ( Site 0422)

    Santiago, Region M. de Santiago, 8330024

  • Sociedad Medica Aren y Bachero Limitada ( Site 0426)

    Santiago, Region M. de Santiago, 8420383

  • Centro Investigación del Cáncer James Lind ( Site 0425)

    Temuco, Araucania, 4780000

  • Oncocentro ( Site 0424)

    Viña del Mar, Valparaiso, 2520598

Other trials in Chile

Poland5 sites

  • Centrum Onkologii im.prof. F. Lukaszczyka w Bydgoszczy ( Site 0273)

    Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-796

  • Uniwersyteckie Centrum Kliniczne ( Site 0281)

    Gdansk, Pomeranian Voivodeship, 80-214

  • Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 0278)

    Gliwice, Silesian Voivodeship, 44-102

  • Pratia MCM Krakow ( Site 0280)

    Krakow, Lesser Poland Voivodeship, 30-510

  • Szpital Kliniczny im. Heliodora Swiecickiego Uniwers Medyczn ( Site 0272)

    Poznan, Greater Poland Voivodeship, 60-780

Other trials in Poland

South Korea4 sites

  • Kyungpook National University Chilgok Hospital ( Site 0553)

    Daegu, Taegu-Kwangyokshi, 41404

  • Seoul National University Hospital ( Site 0554)

    Seoul, 03080

  • Severance Hospital Yonsei University Health System ( Site 0552)

    Seoul, 03722

  • Samsung Medical Center ( Site 0551)

    Seoul, 06351

Other trials in South Korea

Switzerland4 sites

  • Universitaetsspital Basel ( Site 0094)

    Basel, Canton of Basel-City, 4031

  • Kantonsspital Graubuenden ( Site 0091)

    Chur, Kanton Graubünden, 7000

  • Kantonsspital Winterthur ( Site 0095)

    Winterthur, Canton of Zurich, 8401

  • Universitaetsspital Zuerich ( Site 0092)

    Zuerich-Flughafen, Canton of Zurich, 8058

Other trials in Switzerland

United Kingdom4 sites

  • Western General Hospital ( Site 0121)

    Edinburgh, Edinburgh, City of, EH4 2XU

  • Guys and St Thomas NHS Foundation Trust ( Site 0126)

    London, London, City of, SE1 9RT

  • Derriford Hospital ( Site 0129)

    Plymouth, PL6 8DH

  • Singleton Hospital ( Site 0131)

    Swansea, SA2 8QA

Other trials in United Kingdom

South Africa3 sites

  • Sandton Oncology Medical Group PTY LTD ( Site 0802)

    Johannesburg, Gauteng, 2196

  • Cape Town Oncology Trials Pty Ltd ( Site 0803)

    Kraaifontein, Western Cape, 7570

  • Cancer Care Langenhoven Drive Oncology Centre ( Site 0805)

    Port Elizabeth, Eastern Cape, 6045

Other trials in South Africa

Austria2 sites

  • LKH Universitatsklinikum Graz ( Site 0776)

    Graz, Styria, 8036

  • Medizinische Universitat Wien ( Site 0778)

    Vienna, 1090

Other trials in Austria

About this study

Official 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)

The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475) combined with lenvatinib (MK-7902/E7080) compared to pembrolizumab alone (with placebo for lenvatinib) as first-line treatment in adults with no prior systemic therapy for their advanced melanoma.

The primary study hypotheses are that: 1) The combination of pembrolizumab and lenvatinib is superior to pembrolizumab and placebo as assessed by Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), and 2) The combination of pembrolizumab and lenvatinib is superior to pembrolizumab and placebo as assessed by Overall Survival (OS). For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.

Read the detailed description

As of 03-April-2023 active participants, investigator, and sponsor personnel or delegate(s) involved in the treatment administration or clinical evaluation of the participants will be unblinded.

Being tested
Pembrolizumab, Lenvatinib, Placebo for lenvatinib
Keywords
programmed cell death 1 (PD-1, PD1), programmed cell death-ligand 1 (PD-L1, PDL1), programmed cell death-ligand 2 (PD-L2, PDL2)
Medical subject headings
Melanoma, Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

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

  • PembrolizumabBiological

    Also called MK-3475, KEYTRUDA®

    IV infusion

  • LenvatinibDrug

    Also called MK-7902, E7080, LENVIMA®

    Oral capsule

  • Placebo for lenvatinibDrug

    Oral capsule

Study groups in NCT03820986
Study groupRoleWhat they receive
Pembrolizumab+LenvatinibExperimentalParticipants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule daily for up to at least 2 years.
Receives: Biological: Pembrolizumab; Drug: Lenvatinib
Pembrolizumab+PlaceboActive comparatorParticipants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule daily for up to at least 2 years.
Receives: Biological: Pembrolizumab; Drug: Placebo for lenvatinib

What is being measured

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

  1. Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

    PFS is defined as the time from date of randomization to the date of the first documentation of progressive disease (PD) or death from any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions is also considered PD. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The final analysis for this outcome is presented here.

    Measured: Up to approximately 34 months

  2. Overall Survival (OS)

    OS is defined as the time from date of randomization to date of death from any cause. The final analysis for this outcome is presented here.

    Measured: Up to approximately 46 months

Secondary outcomes (8)

  1. Objective Response Rate (ORR) as Assessed by BICR Per RECIST 1.1

    ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The final analysis for this outcome is presented here.

    Measured: Up to approximately 46 months

  2. Duration of Response (DOR) as Assessed by BICR Per RECIST 1.1

    For participants who demonstrated CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), DOR is defined as the date of the first documented evidence of CR or PR until disease progression or death from any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions is also considered PD. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The final analysis for this outcome is presented here.

    Measured: Up to approximately 46 months

  3. Number of Participants With Adverse Events (AEs)

    An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The final analysis for this outcome is presented here.

    Measured: Up to approximately 67 months

  4. Number of Participants Who Discontinue Study Treatment Due to Adverse Events (AEs)

    An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinued any study treatment due to an AE is presented. The final analysis for this outcome is presented here.

    Measured: Up to approximately 63 months

  5. Change From Baseline in European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire-Core 30 [QLQ-C30] Global Health Status (GHS)/Quality of Life (QoL) Score

    The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The GHS/QoL combined score consists of participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" GHS/QoL responses range in score from 0 to 100, with a higher score indicating a better outcome. The final analysis for this outcome is presented here.

    Measured: Baseline and Week 21

  6. Change From Baseline in European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire-Core 30 [QLQ-C30] Physical Function (PF) Score

    The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The PF Score consists of participant responses to questions regarding PF (5 questions about daily activities [strenuous activities, long walks, short walks, bed/chair rest and needing help with eating, dressing, washing themselves or using the toilet]). For PF, responses range in score from 0 to 100, with a higher score indicating a better outcome. The final analysis for this outcome is presented here.

    Measured: Baseline and Week 21

  7. Time to True Deterioration (TTD) Based on Change From Baseline in EORTC QLQ-C30 GHS/QoL Score

    TTD is defined as the time from Baseline to 1st onset of a ≥10-point negative change (decrease) in EORTC-QLQ-C30 GHS Score. The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The GHS/QoL Score consists of participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" GHS/QoL responses range in score from 0 to 100, with a higher score indicating a better outcome. A longer TTD indicates a better outcome. The final analysis for this outcome is presented here.

    Measured: Up to approximately 30 months

  8. Time to True Deterioration (TTD) Based on Change From Baseline in EORTC QLQ-C30 in Physical Function (PF) Score

    TTD is defined as the time from Baseline to 1st onset of a ≥10-point negative change (decrease) in EORTC-QLQ-C30 PF Score. The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The PF Score consists of participant responses to questions regarding PF (5 questions about daily activities [strenuous activities, long walks, short walks, bed/chair rest \& needing help with eating, dressing, washing themselves or using the toilet]. For PF, responses range in score from 0 to 100, with a higher score indicating a better outcome. The final analysis for this outcome is presented here.

    Measured: Up to approximately 30 months

Timeline

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

  1. First posted29 Jan 2019
  2. Study start12 Mar 2019
  3. Primary completion18 Jan 2023
  4. Study completion1 Nov 2024

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
674 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03820986
Sponsor's protocol ID
7902-003
Other IDs
MK-7902-003, E7080-G000-312, LEAP-003, 2018-002520-16, 2018
Status last verified
Jan 2026
First submitted
22 Jan 2019
Last updated
9 Feb 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

  • Arance A, Berciano-Guerrero MA, Guo J, Carlino MS, Ascierto PA, Burotto M, Mortier L, Queirolo P, Chiarion-Sileni V, Schachter J, Zhang X, Martin-Liberal J, Del Vecchio M, Okpara CE, Dutcus C, Zhang J, Diede SJ, Neff T, Long GV. Randomized, double-blind, phase III LEAP-003 study of first-line lenvatinib plus pembrolizumab versus placebo plus pembrolizumab for unresectable or metastatic melanoma. Ann Oncol. 2025 Dec;36(12):1535-1546. doi: 10.1016/j.annonc.2025.08.008. Epub 2025 Aug 28.

    PubMed 40885529

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pembrolizumab and Lenvatinib in people with Malignant Melanoma, run by Merck Sharp & Dohme LLC at 119 sites in 18 countries.

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 17 inclusion and 30 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: finished, as of the sponsor's last update on 9 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 119 sites in United States, China, France, Spain, Germany and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) (time frame: Up to approximately 34 months). The study lists 2 primary outcomes in all. 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 NCT03820986, which also lists 1 linked publication.

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 9 Feb 2026.

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