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 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Malignant Melanoma
• Intervention / Treatment: Biological: Pembrolizumab; Drug: Lenvatinib; Drug: Placebo for lenvatinib

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.

• Study Type: Interventional
• Enrollment (Actual): 674
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Lismore, Australian Capital Territory, Australia, 2480
      • Lismore Base Hospital ( Site 0453)
  • New South Wales
    • North Sydney, New South Wales, Australia, 2060
      • Melanoma Institute Australia ( Site 0452)
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital ( Site 0451)
  • Queensland
    • Wooloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital ( Site 0454)
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Eastern Health ( Site 0457)
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital ( Site 0456)
• Austria
  • Wien, Austria, 1090
    • Medizinische Universitat Wien ( Site 0778)
  • Steiermark
    • Graz, Steiermark, Austria, 8036
      • LKH Universitatsklinikum Graz ( Site 0776)
• Brazil
  • Rio de Janeiro, Brazil, 20220-410
    • Instituto Nacional de Cancer Hospital do Cancer II ( Site 0394)
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30130-090
      • PERSONAL - Oncologia de Precisao e Personalizada ( Site 0399)
  • Rio Grande Do Sul
    • Ijui, Rio Grande Do Sul, Brazil, 98700-000
      • Hospital de Caridade de Ijui ( Site 0391)
    • Passo Fundo, Rio Grande Do Sul, Brazil, 99010-080
      • Hospital Sao Vicente de Paulo ( Site 0396)
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
      • Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0397)
• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
      • BC Cancer-Kelowna - Sindi Ahluwalia Hawkins Centre ( Site 0661)
    • North Vancouver, British Columbia, Canada, V7L 2L7
      • Lions Gate Hospital ( Site 0662)
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Research Institute ( Site 0654)
  • Quebec
    • Montreal, Quebec, Canada, H2W 3E4
      • Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0652)
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre ( Site 0651)
• Chile
  • Araucania
    • Temuco, Araucania, Chile, 4780000
      • Centro Investigación del Cáncer James Lind ( Site 0425)
  • Region M. De Santiago
    • Santiago, Region M. De Santiago, Chile, 7500921
      • Fundacion Arturo Lopez Perez FALP ( Site 0421)
    • Santiago, Region M. De Santiago, Chile, 8330024
      • Pontificia Universidad Catolica de Chile ( Site 0422)
    • Santiago, Region M. De Santiago, Chile, 8420383
      • Sociedad Medica Aren y Bachero Limitada ( Site 0426)
  • Valparaiso
    • Vina del Mar, Valparaiso, Chile, 2520598
      • Oncocentro ( Site 0424)
• China
  • Beijing
    • Beijing, Beijing, China, 100036
      • Beijing Cancer Hospital ( Site 0601)
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Provincial Cancer Hospital ( Site 0612)
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Sun Yat-Sen University Cancer Center ( Site 0602)
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Henan Cancer Hospital ( Site 0610)
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Nanjing Drum Tower Hospital ( Site 0609)
  • Jilin
    • Chang Chun, Jilin, China, 130021
      • The First Hospital Of Jilin University ( Site 0603)
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Shanghai Cancer Center ( Site 0607)
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute & Hospital ( Site 0606)
  • Yunnan
    • Kunming, Yunnan, China, 430030
      • Yunnan Cancer Hospital ( Site 0604)
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310018
      • Sir Run Run Shaw Hospital ( Site 0605)
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital ( Site 0608)
• France
  • Alpes-Maritimes
    • Nice, Alpes-Maritimes, France, 06200
      • Hopital ARCHET 2 ( Site 0009)
  • Bouches-du-Rhone
    • Marseille, Bouches-du-Rhone, France, 13385
      • Hopital La Timone ( Site 0002)
  • Cote-d Or
    • Dijon, Cote-d Or, France, 21079
      • CHU Dijon Bourgogne ( Site 0010)
  • Haute-Garonne
    • Toulouse, Haute-Garonne, France, 31059
      • Institut Claudius Regaud IUCT Oncopole ( Site 0003)
  • Hauts-de-Seine
    • Boulogne-Billancourt, Hauts-de-Seine, France, 92100
      • Hopital Ambroise Pare Boulogne ( Site 0007)
  • Nord
    • Lille, Nord, France, 59037
      • CHRU Lille - Hopital Claude Huriez ( Site 0004)
  • Seine-Maritime
    • Rouen, Seine-Maritime, France, 76000
      • CHU de Rouen ( Site 0013)
  • Val-d Oise
    • Argenteuil, Val-d Oise, France, 95100
      • Centre Hospitalier Victor Dupouy ( Site 0012)
  • Val-de-Marne
    • Villejuif, Val-de-Marne, France, 94805
      • Institut Gustave Roussy ( Site 0001)
  • Vienne
    • Poitiers, Vienne, France, 86021
      • CHU de la Miletrie Poitiers ( Site 0011)
• Germany
  • Baden-Wurttemberg
    • Hannover, Baden-Wurttemberg, Germany, 30625
      • Klinik fur Dermatologie Allergologie und Venerologie ( Site 0035)
  • Bayern
    • Erlangen, Bayern, Germany, 91054
      • Universitaetsklinikum Erlangen ( Site 0044)
    • Wuerzburg, Bayern, Germany, 97080
      • Universitaetsklinikum Wuerzburg-Department of Dermatology ( Site 0036)
  • Niedersachsen
    • Buxtehude, Niedersachsen, Germany, 21614
      • Hautkrebszentrum Buxtehude ( Site 0037)
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • Universitaetsklinikum Carl Gustav Carus ( Site 0041)
    • Leipzig, Sachsen, Germany, 04103
      • Universitaetsklinikum Leipzig ( Site 0040)
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
      • Universitaetsklinikum Schleswig-Holstein Campus Kiel ( Site 0033)
  • Thuringen
    • Gera, Thuringen, Germany, 07548
      • SRH Wald-Klinikum Gera GmbH ( Site 0042)
• Israel
  • Afula, Israel, 1834111
    • HaEmek Medical Center ( Site 0306)
  • Beer Sheva, Israel, 8457108
    • Soroka Medical Center ( Site 0303)
  • Haifa, Israel, 3109601
    • Rambam Medical Center ( Site 0301)
  • Jerusalem, Israel, 9112001
    • Hadassah Ein Karem Hebrew University Medical Center ( Site 0305)
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center ( Site 0302)
  • Ramat Gan, Israel, 5262000
    • Chaim Sheba Medical Center ( Site 0304)
  • Tel Aviv, Israel, 6423906
    • Sourasky Medical Center ( Site 0307)
  • Zerifin, Israel, 70300
    • Shamir Medical Center-Assaf Harofeh ( Site 0308)
• Italy
  • Milano, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0064)
  • Milano, Italy, 20141
    • Istituto Europeo di Oncologia ( Site 0067)
  • Napoli, Italy, 80131
    • Istituto Nazionale Tumori Fondazione Pascale ( Site 0061)
  • Padova, Italy, 35128
    • Istituto Oncologico Veneto ( Site 0063)
  • Abruzzo
    • Bergamo, Abruzzo, Italy, 24127
      • ASST Papa Giovanni XXIII ( Site 0062)
  • Toscana
    • Siena, Toscana, Italy, 53100
      • Azienda Ospedaliera Universitaria Senese ( Site 0065)
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital ( Site 0554)
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital Yonsei University Health System ( Site 0552)
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center ( Site 0551)
  • Taegu-Kwangyokshi
    • Daegu, Taegu-Kwangyokshi, Korea, Republic of, 41404
      • Kyungpook National University Chilgok Hospital ( Site 0553)
• Poland
  • Kujawsko-pomorskie
    • Bydgoszcz, Kujawsko-pomorskie, Poland, 85-796
      • Centrum Onkologii im.prof. F. Lukaszczyka w Bydgoszczy ( Site 0273)
  • Malopolskie
    • Krakow, Malopolskie, Poland, 30-510
      • Pratia MCM Krakow ( Site 0280)
  • Pomorskie
    • Gdansk, Pomorskie, Poland, 80-214
      • Uniwersyteckie Centrum Kliniczne ( Site 0281)
  • Slaskie
    • Gliwice, Slaskie, Poland, 44-102
      • Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 0278)
  • Wielkopolskie
    • Poznan, Wielkopolskie, Poland, 60-780
      • Szpital Kliniczny im. Heliodora Swiecickiego Uniwers Medyczn ( Site 0272)
• South Africa
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa, 6045
      • Cancer Care Langenhoven Drive Oncology Centre ( Site 0805)
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2196
      • Sandton Oncology Medical Group PTY LTD ( Site 0802)
  • Western Cape
    • Kraaifontein, Western Cape, South Africa, 7570
      • Cape Town Oncology Trials Pty Ltd ( Site 0803)
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial Barcelona ( Site 0190)
  • Madrid, Spain, 28009
    • Hospital General Universitario Gregorio Maranon ( Site 0191)
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal ( Site 0183)
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz ( Site 0184)
  • Malaga, Spain, 29010
    • Hospital Universitario Carlos Haya ( Site 0186)
  • Barcelona
    • Hospitalet del Llobregat, Barcelona, Spain, 08908
      • Hospital Duran i Reinals ICO de Hospitalet ( Site 0187)
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques de Valdecilla ( Site 0181)
  • La Coruna
    • A Coruna, La Coruna, Spain, 15006
      • Complejo Hospitalario Universitario A Coruna. CHUAC ( Site 0182)
  • Las Palmas
    • Las Palmas de Gran Canaria, Las Palmas, Spain, 35001
      • Hospital Universitario Insular de Gran Canaria ( Site 0189)
• Sweden
  • Jonkopings Lan
    • Jonkoping, Jonkopings Lan, Sweden, 551 85
      • Laenssjukhuset Ryhov ( Site 0215)
  • Kronobergs Lan
    • Vaxjo, Kronobergs Lan, Sweden, 351 85
      • Centrallasarettet Vaxjo ( Site 0214)
  • Skane Lan
    • Lund, Skane Lan, Sweden, 221 85
      • Skanes Universitetssjukhus ( Site 0213)
  • Stockholms Lan
    • Solna, Stockholms Lan, Sweden, 171 64
      • Karolinska Universitetssjukhuset ( Site 0211)
  • Uppsala Lan
    • Uppsala, Uppsala Lan, Sweden, 751 85
      • Akademiska Sjukhuset ( Site 0218)
  • Vasterbottens Lan
    • Umea, Vasterbottens Lan, Sweden, 901 85
      • Norrlands Universitetssjukhus ( Site 0216)
  • Vastra Gotalands Lan
    • Goteborg, Vastra Gotalands Lan, Sweden, 413 45
      • Sahlgrenska Universitetssjukhuset ( Site 0212)
• Switzerland
  • Basel-Stadt
    • Basel, Basel-Stadt, Switzerland, 4031
      • Universitaetsspital Basel ( Site 0094)
  • Grisons
    • Chur, Grisons, Switzerland, 7000
      • Kantonsspital Graubuenden ( Site 0091)
  • Zurich
    • Winterthur, Zurich, Switzerland, 8401
      • Kantonsspital Winterthur ( Site 0095)
    • Zuerich-Flughafen, Zurich, Switzerland, 8058
      • Universitaetsspital Zuerich ( Site 0092)
• United Kingdom
  • Plymouth, United Kingdom, PL6 8DH
    • Derriford Hospital ( Site 0129)
  • Swansea, United Kingdom, SA2 8QA
    • Singleton Hospital ( Site 0131)
  • Edinburgh, City Of
    • Edinburgh, Edinburgh, City Of, United Kingdom, EH4 2XU
      • Western General Hospital ( Site 0121)
  • London, City Of
    • London, London, City Of, United Kingdom, SE1 9RT
      • Guys and St Thomas NHS Foundation Trust ( Site 0126)
• United States
  • California
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Research Institute ( Site 0707)
    • San Francisco, California, United States, 30322
      • UCSF Helen Diller Family Comprehensive Cancer Center ( Site 0704)
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center Research Institute ( Site 0705)
    • Santa Monica, California, United States, 90404
      • John Wayne Cancer Institute ( Site 0706)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center ( Site 0708)
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale Cancer Center ( Site 0709)
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist MD Anderson Cancer Center ( Site 0767)
    • Orange City, Florida, United States, 32763
      • Mid-Florida Cancer Centers ( Site 0764)
  • Illinois
    • Park Ridge, Illinois, United States, 60068
      • AMG Oncology ( Site 0714)
    • Peoria, Illinois, United States, 61615
      • Illinois Cancer Care, PC ( Site 0765)
  • Minnesota
    • Fridley, Minnesota, United States, 55432
      • Minnesota Oncology Specialist, PA ( Site 0766)
  • Montana
    • Billings, Montana, United States, 59102
      • St. Vincent Frontier Cancer Center ( Site 0724)
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Atlantic Health System ( Site 0768)
    • Paramus, New Jersey, United States, 07652
      • Valley Hospital ( Site 0749)
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina - Cancer Hospital ( Site 0751)
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU Center for Health & Healing ( Site 0731)
  • Virginia
    • Fairfax, Virginia, United States, 22031-4867
      • Inova Schar Cancer Institute ( Site 0739)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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:

  1. 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/MEKi therapy are eligible to participate in this study after discussion with the medical monitor.
  2. 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).
• 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:

  1. Not a woman of childbearing potential (WOCBP). OR
  2. 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.

Exclusion Criteria:

• 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.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pembrolizumab+Lenvatinib; Participants 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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; KEYTRUDA®; Drug: Lenvatinib; Oral capsule; Other Names: E7080; MK-7902; LENVIMA®
Active Comparator: Pembrolizumab+Placebo; Participants 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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; KEYTRUDA®; Drug: Placebo for lenvatinib; Oral capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to approximately 46 months
Overall Survival (OS)	OS is defined as the time from date of randomization to date of death from any cause.	Up to approximately 46 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to approximately 46 months
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.	Up to approximately 46 months
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.	Up to approximately 46 months
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.	Up to approximately 46 months
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.	Baseline and Week 21
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.	Baseline and Week 21
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. TThe 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	Up to approximately 30 months
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.	Up to approximately 30 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Collaborators: Eisai Inc.
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trial Information

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2019
• Primary Completion (Actual): January 18, 2023
• Study Completion (Estimated): November 8, 2024

Study Registration Dates

• First Submitted: January 22, 2019
• First Submitted That Met QC Criteria: January 25, 2019
• First Posted (Actual): January 29, 2019

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: programmed cell death 1 (PD-1, PD1); programmed cell death-ligand 1 (PD-L1, PDL1); programmed cell death-ligand 2 (PD-L2, PDL2)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Immune Checkpoint Inhibitors; Pembrolizumab; Lenvatinib
• Other Study ID Numbers: 7902-003; MK-7902-003 (Other Identifier: Merck Protocol Number); E7080-G000-312 (Other Identifier: Eisai Protocol Number); LEAP-003 (Other Identifier: Merck); 2018-002520-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No