Safety and Efficacy of Lenvatinib (E7080/MK-7902) in Combination With Pembrolizumab (MK-3475) Versus Lenvatinib as First-line Therapy in Participants With Advanced Hepatocellular Carcinoma (MK-7902-002/E7080-G000-311/LEAP-002)

A Phase 3 Multicenter, Randomized, Double-blinded, Active-controlled, Clinical Study to Evaluate the Safety and Efficacy of Lenvatinib (E7080/MK-7902) in Combination With Pembrolizumab (MK-3475) Versus Lenvatinib in First-line Therapy of Participants With Advanced Hepatocellular Carcinoma (LEAP-002)

The purpose of this study is to evaluate the safety and efficacy of lenvatinib (E7080/MK-7902) in combination with pembrolizumab (MK-3745) versus lenvatinib in combination with placebo as first-line therapy for the treatment of advanced hepatocellular carcinoma in adult participants.

The primary hypotheses of this study are that lenvatinib plus pembrolizumab is superior to lenvatinib plus placebo with respect to progression-free survival (PFS) and overall survival (OS).

Study Overview

• Status: Active, not recruiting
• Conditions: Carcinoma, Hepatocellular
• Intervention / Treatment: Drug: lenvatinib; Biological: pembrolizumab; Drug: saline placebo

• Study Type: Interventional
• Enrollment (Actual): 794
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Liverpool, Australia, 2170
    • Liverpool Hospital. ( Site 0002)
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital ( Site 0001)
  • Queensland
    • Wooloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital ( Site 0007)
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health-Monash Medical Centre ( Site 0004)
    • Fitzroy, Victoria, Australia, 3065
      • St Vincents Hospital Melbourne ( Site 0003)
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BC Cancer-Vancouver Center ( Site 0056)
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre ( Site 0053)
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Research Institute ( Site 0055)
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre ( Site 0050)
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre ( Site 0052)
• Chile
  • Temuco, Chile, 4810469
    • Instituto Clinico Oncologico del Sur ( Site 0067)
  • Region Del Maule
    • Talca, Region Del Maule, Chile, 3465584
      • Clinica Universidad Catolica del Maule ( Site 0065)
  • Region Metropolitana De Santiago
    • Santiago, Region Metropolitana De Santiago, Chile, 7500921
      • Fundacion Arturo Lopez Perez ( Site 0064)
    • Santiago, Region Metropolitana De Santiago, Chile, 8330024
      • Pontificia Universidad Catolica de Chile ( Site 0070)
• China
  • Shanghai, China, 200032
    • Zhongshan Hospital Fudan University ( Site 0096)
  • Anhui
    • Hefei, Anhui, China, 230088
      • First Affiliated Hospital of Anhui Medical University ( Site 0095)
  • Beijing
    • Beijing, Beijing, China, 100021
      • Cancer Hospital Chinese Academy of Medical Sciences ( Site 0100)
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital ( Site 0088)
  • Fujian
    • Fuzhou, Fujian, China, 350025
      • 900 Hospital of the Joint ( Site 0091)
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong General Hospital ( Site 0092)
    • Guangzhou, Guangdong, China, 510515
      • Southern Medical University Nanfang Hospital ( Site 0102)
  • Heilongjiang
    • Harbin, Heilongjiang, China, 610000
      • Harbin Medical University Cancer Hospital ( Site 0089)
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Wuhan Union hospital Cancer Center ( Site 0105)
  • Hunan
    • Changsha, Hunan, China, 410006
      • Hunan Cancer Hospital ( Site 0094)
    • Changsha, Hunan, China, 410013
      • The Third Xiangya Hospital of Central South University ( Site 0093)
  • Jiangsu
    • Nanjing, Jiangsu, China, 210031
      • The 81st Hospital of PLA ( Site 0085)
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Shanghai Cancer Center ( Site 0086)
  • Shanxi
    • XI An, Shanxi, China, 710061
      • The First Affiliated Hospital of Xi an Jiaotong University ( Site 0090)
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • West China Hospital of Sichuan University ( Site 0087)
  • Xinjiang
    • Urumqi, Xinjiang, China, 830001
      • Affiliated Tumor Hospital of Xinjiang Medical University ( Site 0109)
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital of Zhejiang University ( Site 0097)
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital ( Site 0110)
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital ( Site 0101)
• Colombia
  • Antioquia
    • Medellin, Antioquia, Colombia, 050021
      • Fundacion Centro de Investigacion Clinica CIC ( Site 0141)
    • Medellin, Antioquia, Colombia, 050034
      • Hospital Pablo Tobon Uribe ( Site 0144)
    • Medellin, Antioquia, Colombia, 500515
      • Hospital General de Medellin Luz Castro de Gutierrez ( Site 0137)
  • Atlantico
    • Barranquilla, Atlantico, Colombia, 080002
      • Biomelab S A S ( Site 0145)
  • Distrito Capital De Bogota
    • Bogota, Distrito Capital De Bogota, Colombia, 110221
      • Administradora Country SA - Clinica del Country ( Site 0146)
    • Bogota, Distrito Capital De Bogota, Colombia, 111511
      • Instituto Nacional de Cancerologia E.S.E ( Site 0142)
  • Valle Del Cauca
    • Cali, Valle Del Cauca, Colombia, 760032
      • Fundacion Valle del Lili ( Site 0140)
    • Cali, Valle Del Cauca, Colombia, 760042
      • Centro Medico Imbanaco de Cali S.A ( Site 0139)
• France
  • Avignon, France, 84918
    • Institut Sainte Catherine ( Site 0167)
  • Clichy, France, 92110
    • Hopital Beaujon ( Site 0160)
  • Creteil, France, 94000
    • CHU Henri Mondor ( Site 0162)
  • Lille, France, 59037
    • CHRU de Lille - Hopital Claude Huriez ( Site 0159)
  • Lyon, France, 69004
    • Hopital de la Croix Rousse ( Site 0157)
  • Marseille, France, 13285
    • Hopital Saint Joseph ( Site 0166)
  • Orleans, France, 45100
    • Centre Hospitalier Regional du Orleans ( Site 0169)
  • Rennes, France, 35042
    • Centre Eugene Marquis ( Site 0158)
  • Vandoeuvre les Nancy, France, 54500
    • CHU de Nancy Hopital Brabois Adultes ( Site 0164)
• Germany
  • Aachen, Germany, 52074
    • Klinikum der Universitaet Aachen - RWTH ( Site 0185)
  • Dresden, Germany, 01307
    • Universitaetsklinikum Carl Gustav Carus der TU Dresden ( Site 0178)
  • Essen, Germany, 45147
    • Universitaetsklinikum Essen ( Site 0188)
  • Frankfurt am Main, Germany, 60596
    • Universitaetsklinikum Frankfurt ( Site 0180)
  • Hamburg, Germany, 20246
    • Universitaetsklinikum Hamburg-Eppendorf ( Site 0184)
  • Koeln, Germany, 50937
    • Universitaetsklinik Koeln ( Site 0189)
  • Leipzig, Germany, 04103
    • Universitaetsklinikum Leipzig ( Site 0187)
  • Magdeburg, Germany, 39120
    • Otto-Von-Guericke-Universitaet Magdeburg ( Site 0182)
  • Tuebingen, Germany, 72076
    • Universitaetsklinikum Tuebingen ( Site 0179)
  • Wuerzburg, Germany, 97080
    • Universitaetsklinikum Wuerzburg ( Site 0186)
• Ireland
  • Dublin, Ireland, D04 T6F4
    • St Vincents University Hospital ( Site 0242)
  • Dublin, Ireland, D07 R2WY
    • Mater Misericordiae University Hospital ( Site 0241)
• Italy
  • Aviano, Italy, 33081
    • Centro di Riferimento Oncologico de Aviano Istituto Nazionale Tumori ( Site 0292)
  • Bologna, Italy, 40138
    • Policlinico S. Orsola-Malpighi ( Site 0286)
  • Padova, Italy, 35128
    • Istituto Oncologico Veneto ( Site 0287)
  • Palermo, Italy, 90127
    • Az Osp Univ Policlin Paolo Giaccone ( Site 0284)
  • Pavia, Italy, 27100
    • Fondazione Salvatore Maugeri IRCCS. ( Site 0290)
  • Pisa, Italy, 56126
    • Azienda Ospedaliero-Univers. Pisana Ospedale S. Chiara ( Site 0291)
  • Roma, Italy, 00128
    • Policlinico Universitario Campus Biomedico ( Site 0288)
  • VR
    • Negrar, VR, Italy, 37024
      • Ospedale Sacro Cuore - Don Calabria ( Site 0289)
• Japan
  • Chiba, Japan, 260-8677
    • Chiba University Hospital ( Site 0305)
  • Fukuoka, Japan, 810-8563
    • National Hospital Organization Kyushu Medical Center ( Site 0321)
  • Hiroshima, Japan, 734-8551
    • Hiroshima University Hospital ( Site 0320)
  • Osaka, Japan, 543-8555
    • Osaka Red Cross Hospital ( Site 0317)
  • Saga, Japan, 840-8571
    • Saga-Ken Medical Centre Koseikan ( Site 0323)
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital ( Site 0307)
  • Tokyo, Japan, 105-8470
    • Toranomon Hospital ( Site 0311)
  • Tokyo, Japan, 113-8655
    • The University of Tokyo Hospital ( Site 0308)
  • Wakayama, Japan, 641-8510
    • Wakayama Medical University Hospital ( Site 0318)
  • Aichi
    • Nagoya, Aichi, Japan, 464-8681
      • Aichi Cancer Center Hospital ( Site 0316)
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East ( Site 0306)
  • Fukuoka
    • Kurume, Fukuoka, Japan, 830-0011
      • Kurume University Hospital ( Site 0322)
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-0033
      • Hokkaido P.W.F.A.C Sapporo-Kosei General Hospital ( Site 0304)
  • Ishikawa
    • Kanazawa, Ishikawa, Japan, 920-8641
      • Kanazawa University Hospital ( Site 0315)
  • Kagawa
    • Kita-gun, Kagawa, Japan, 761-0793
      • Kagawa University Hospital ( Site 0324)
    • Takamatsu, Kagawa, Japan, 760-8557
      • Kagawa Prefectural Central Hospital ( Site 0325)
  • Kanagawa
    • Kawasaki, Kanagawa, Japan, 213-8587
      • Toranomon Hospital Kajigaya ( Site 0312)
    • Yokohama, Kanagawa, Japan, 232-0024
      • Yokohama City University Medical Center ( Site 0313)
    • Yokohama, Kanagawa, Japan, 241-8515
      • Kanagawa Cancer Center ( Site 0314)
  • Osaka
    • Osakasayama, Osaka, Japan, 589-8511
      • Kindai University Hospital ( Site 0319)
  • Tokyo
    • Mitaka, Tokyo, Japan, 181-8611
      • Kyorin University Hospital ( Site 0309)
    • Musashino, Tokyo, Japan, 180-8610
      • Musashino Red Cross Hospital ( Site 0310)
• Korea, Republic of
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center ( Site 0461)
  • Kyonggi-do
    • Seongnam-si, Kyonggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital ( Site 0464)
  • Seoul-teukbyeolsi [Seoul]
    • Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of, 03080
      • Seoul National University Hospital ( Site 0462)
    • Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of, 03722
      • Yonsei University Severance Hospital ( Site 0463)
    • Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of, 05505
      • Asan Medical Center ( Site 0460)
• Mexico
  • Aguascalientes, Mexico, 20116
    • Centro de Investigacion Medica Aguascalientes ( Site 0355)
  • Merida, Mexico, 97070
    • Medical Care and Research S.A. de C.V. ( Site 0359)
  • Mexico City, Mexico, 06100
    • CRYPTEX Investigacion Clinica S.A. de C.V. ( Site 0362)
  • Oaxaca, Mexico, 68000
    • Oaxaca Site Management Organization S.C. ( Site 0366)
  • Puebla, Mexico, 72530
    • Unidad Medica Oncologica ( Site 0369)
  • Cdmx
    • Ciudad de Mexico, Cdmx, Mexico, 14080
      • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 0363)
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 0365)
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital ( Site 0376)
  • Christchurch, New Zealand, 8011
    • Christchurch Hospital ( Site 0377)
• Poland
  • Myslowice, Poland, 41-400
    • ID Clinic ( Site 0431)
  • Pila, Poland, 64-920
    • Ars Medical Sp. z o.o. ( Site 0433)
  • Warsaw, Poland, 02-106
    • MTZ Clinical Research Sp. z o. o. ( Site 0427)
  • Warszawa, Poland, 02-034
    • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0418)
  • Slaskie
    • Bytom, Slaskie, Poland, 41-902
      • Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu ( Site 0419)
  • Zachodniopomorskie
    • Koszalin, Zachodniopomorskie, Poland, 75-581
      • Szpital Wojewodzki w Koszalinie im. Mikolaja Kopernika ( Site 0421)
• Russian Federation
  • Krasnoyarsk, Russian Federation, 660133
    • Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0450)
  • Pyatigorsk, Russian Federation, 357502
    • Pyatigorsk Oncology Dispensary ( Site 0441)
  • Moskva
    • Moscow, Moskva, Russian Federation, 115478
      • N.N. Blokhin NMRCO ( Site 0439)
    • Moscow, Moskva, Russian Federation, 119881
      • First Moscow State Medical University n.a. I.M.Sechenov ( Site 0453)
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 195271
      • Railway Hospital of OJSC ( Site 0447)
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 198255
      • City Clinical Oncology Center ( Site 0446)
• Spain
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon ( Site 0504)
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal ( Site 0514)
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz ( Site 0510)
  • Santiago de Compostela, Spain, 15706
    • Complejo Hospitalario Universitario de Santiago ( Site 0506)
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio ( Site 0509)
  • Valencia, Spain, 46026
    • Hospital Universitario y Politecnico La Fe de Valencia ( Site 0505)
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08035
      • Hospital Universitari Vall d Hebron ( Site 0508)
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro ( Site 0513)
• Taiwan
  • Kaoshiung, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital ( Site 0529)
  • Taichung, Taiwan, 404
    • China Medical University Hospital ( Site 0527)
  • Taichung, Taiwan, 407
    • Taichung Veterans General Hospital ( Site 0526)
  • Tainan, Taiwan, 70457
    • National Cheng Kung University Hospital ( Site 0528)
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital ( Site 0523)
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital ( Site 0524)
  • Taoyuan, Taiwan, 333
    • Chang Gung Medical Foundation. Linkou ( Site 0525)
• Thailand
  • Chiang Mai, Thailand, 50200
    • Chiang Mai University Maharaj Nakorn Chiang Mai Hospital ( Site 0211)
  • Bangkok
    • Bangkok Noi, Bangkok, Thailand, 10700
      • Siriraj Hospital. Mahidol Univerisity ( Site 0213)
  • Songkhla
    • HatYai, Songkhla, Thailand, 90110
      • Songklanagarind Hospital ( Site 0214)
• Turkey
  • Adana, Turkey, 01250
    • Adana Sehir Hastanesi ( Site 0549)
  • Ankara, Turkey, 06100
    • Hacettepe Uni. Tip Fakultesi ( Site 0553)
  • Ankara, Turkey, 06200
    • Abdurrahman Yurtaslan Onkoloji Hastanesi ( Site 0551)
  • Antalya, Turkey, 07070
    • Akdeniz Universitesi Tip Fakultesi ( Site 0548)
  • Edirne, Turkey, 22030
    • Trakya Universitesi Tip Fakultesi ( Site 0544)
  • Erzurum, Turkey, 25240
    • Erzurum Ataturk University Faculty of Medicine ( Site 0546)
  • Konya, Turkey, 42080
    • Necmettin Erbakan Universitesi Meram Tip Fakultesi ( Site 0550)
  • Malatya, Turkey, 44280
    • Inonu Universitesi Medical Fakultesi ( Site 0545)
  • İstanbul, Turkey, 34093
    • Bezmi Alem Universitesi Tıp Fakultesi ( Site 0547)
• United Kingdom
  • Birkenhead, United Kingdom, CH63 4JY
    • The Clatterbridge Cancer Centre NHS Foundation Trust ( Site 0573)
  • Glasgow, United Kingdom, G12 0YN
    • The Beatson West of Scotland Cancer Centre ( Site 0566)
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust ( Site 0575)
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham University Hospitals NHS Trust ( Site 0569)
  • London, City Of
    • London, London, City Of, United Kingdom, NW3 2QG
      • Royal Free London NHS Foundation Trust ( Site 0567)
    • London, London, City Of, United Kingdom, SE5 9RS
      • Kings College Hospital NHS Foundation Trust ( Site 0565)
• United States
  • Arizona
    • Tucson, Arizona, United States, 85721
      • The University of Arizona Cancer Center - North Campus ( Site 0621)
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center ( Site 0587)
    • La Jolla, California, United States, 92037
      • Scripps Health ( Site 0644)
    • San Francisco, California, United States, 94115
      • Pacific Hematology Oncology Associates ( Site 0588)
    • Santa Monica, California, United States, 90404
      • UCLA ( Site 0589)
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University ( Site 0594)
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami, Sylvester Comprehensive Cancer Center ( Site 0596)
    • Orlando, Florida, United States, 32804
      • Advent Health ( Site 0595)
    • Tampa, Florida, United States, 33606
      • Tampa General Medical Group ( Site 0629)
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Winship Cancer Institute ( Site 0639)
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Cancer Center ( Site 0600)
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital ( Site 0603)
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center ( Site 0716)
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai ( Site 0611)
    • Rochester, New York, United States, 14642
      • University of Rochester ( Site 0613)
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center - Cancer Center ( Site 0612)
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Science Center ( Site 0625)
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University ( Site 0645)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19124
      • Eastern Regional Medical Center, Inc. ( Site 0626)
  • Texas
    • Temple, Texas, United States, 76504
      • Central Texas Veterans Healthcare System ( Site 0617)
  • Washington
    • Spokane, Washington, United States, 99218
      • Cancer Care Northwest ( Site 0636)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Is male or female and ≥18 years of age at the time of signing the informed consent
• Has a diagnosis of hepatocellular carcinoma confirmed by radiology, histology, or cytology
• 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 Child-Pugh class A liver score
• Has a predicted life expectancy of >3 months
• Has at least one measurable hepatocellular carcinoma (HCC) lesion based on RECIST 1.1 as confirmed by BICR
• Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1
• Participants with hepatitis B will be eligible as long as their virus is well controlled

Exclusion Criteria:

• Has had esophageal or gastric variceal bleeding within the last 6 months
• Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib
• Has a preexisting Grade ≥3 gastrointestinal or non-gastrointestinal fistula
• Has clinically significant hemoptysis from any source or tumor bleeding within 2 weeks prior to the first dose of study intervention
• 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 had major surgery to the liver within 4 weeks prior to the first dose of study intervention
• Has had a minor surgery (ie, simple excision) within 7 days prior to the first dose of study intervention
• Has serious non-healing wound, ulcer, or bone fracture
• Has received any systemic chemotherapy for HCC or chemotherapy for any malignancy in the past 3 years
• Has received prior therapy with an anti-programmed cell death 1 (ant-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti- programmed cell death ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, or CD137)
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years with the exceptions of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that has undergone potentially curative therapy
• Has a known history of, or any evidence of, central nervous system (CNS) metastases and/or carcinomatous meningitis as assessed by local site investigator
• Has severe hypersensitivity (≥Grade 3) to study intervention and/or any of their excipients
• Has an active autoimmune disease that has required systemic treatment in past 2 years
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
• Has urine protein ≥1 grams/24 hours
• Prolongation of corrected QT (QTc) interval to >480 milliseconds (corrected by Fridericia Formula)
• Has left ventricular ejection fraction (LVEF) below the institutional normal range as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO)
• Has an active infection requiring systemic therapy with the exceptions of hepatitis B virus (HBV) or hepatitis C virus (HCV)
• Has a known history of human immunodeficiency virus (HIV) infection
• Has known active tuberculosis (Bacillus tuberculosis)
• 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 a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study intervention
• Has had an allogenic tissue/solid organ transplant

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: lenvatinib plus pembrolizumab; 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.	Drug: lenvatinib; Administered orally once a day; Other Names: E7080; MK-7902; LENVIMA®; Biological: pembrolizumab; Administered as an IV infusion on Day 1 Q3W; Other Names: MK-3475; KEYTRUDA®
Active Comparator: lenvatinib plus placebo; 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.	Drug: lenvatinib; Administered orally once a day; Other Names: E7080; MK-7902; LENVIMA®; Drug: saline placebo; Administered as an IV infusion on Day 1 Q3W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	PFS was defined as the time from the date of the first documentation of disease progression, as determined by blinded independent central review (BICR) per RECIST 1.1 or death due to any cause (whichever occurred first). Disease progression was defined as at least 20 percent (%) increase (including an absolute increase of at least 5 millimeter [mm]) in the sum of diameter of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method.	Up to approximately 41 months
Overall Survival (OS)	OS was defined as the time from randomization until death from any cause	Up to approximately 41 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	ORR was defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1 as assessed by BICR. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.	Up to approximately 41 months
Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	DOR was determined by disease assessment and is defined as the time from the first documented evidence of a response of CR or PR, per RECIST 1.1 as assessed by BICR, until the first documented disease progression or death due to any cause, whichever occurred first. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.	Up to approximately 41 months
Disease Control Rate (DCR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	DCR was defined as the percentage of participants who have a best overall response of CR, PR, or stable disease (SD) per RECIST 1.1 as assessed by BICR. SD must be achieved at ≥6 weeks after randomization to be considered best overall response. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.	Up to approximately 41 months
Time to Disease Progression (TTP) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	TTP was defined as the time from randomization to the first documented disease progression per RECIST 1.1 as assessed by BICR. RECIST 1.1 was modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ were followed.	Up to approximately 41 months
Progression-free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)	PFS was defined as the time from the first dose of study intervention to the first documented progressive disease (PD) per mRECIST by BICR or death due to any cause, whichever occurred first. mRECIST for HCC allowed evaluation of treatment effects that were not reflected in simple total size changes of lesions. Per mRECIST, PD was defined as an increase of at least 20% in the sum of diameters (SODs) of viable (enhancing) target lesions, taking as reference the smallest SODs of viable (enhancing) target lesions recorded since the treatment started.	Up to approximately 41 months
Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)	ORR wass defined as the percentage of participants who have a confirmed complete response (CR: disappearance of any intratumoral arterial enhancement in all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of viable [enhancement in the arterial phase] target lesions, taking as reference the baseline sum of the diameters of target lesions) per mRECIST as assessed by BICR. mRECIST for hepatocellular carcinoma evaluates lesions within the liver parenchyma showing increased contrast enhancement in the arterial phase. A maximum of 10 target lesions and a maximum of 5 target lesions per organ were followed.	Up to approximately 41 months
Duration of Response (DOR) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)	DOR was determined by disease assessment and is defined as the time from the first documented evidence of a response of CR or PR, per mRECIST as assessed by BICR, until the first documented disease progression or death due to any cause, whichever occurs first. mRECIST for hepatocellular carcinoma evaluates lesions within the liver parenchyma showing increased contrast enhancement in the arterial phase. A maximum of 10 target lesions and a maximum of 5 target lesions per organ were followed.	Up to approximately 41 months
Disease Control Rate (DCR) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)	DCR was defined as the percentage of participants who have a best overall response of CR, PR, or SD per mRECIST as assessed by BICR. mRECIST for hepatocellular carcinoma evaluates lesions within the liver parenchyma showing increased contrast enhancement in the arterial phase. SD must be achieved at ≥6 weeks after randomization to be considered best overall response. A maximum of 10 target lesions and a maximum of 5 target lesions per organ were followed.	Up to approximately 41 months
Time to Disease Progression (TTP) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)	TTP was defined as the time from randomization to the first documented disease progression per mRECIST as assessed by BICR. mRECIST for hepatocellular carcinoma evaluates lesions within the liver parenchyma showing increased contrast enhancement in the arterial phase. A maximum of 10 target lesions and a maximum of 5 target lesions per organ were followed.	Up to approximately 41 months
Number of Participants Who Experienced an Adverse Event (AE)	Number of participants who experienced an AE defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study treatment	Up to approximately 41 months
Number of Participants Who Experienced an Serious Adverse Event (SAE)	Number of participants who experienced a SAE defined as an AE that resulted in death, was life threatening, resulting in persistent or significant disability or incapacity, resulting in or prolonged a hospitalization, was a congenital anomaly or birth defect, was a cancer, was associated with an overdose, or was another important medical event	Up to approximately 41 months
Number of Participants Who Experienced an Immune-related Adverse Event (irAE) of Clinical Interest	Number of participants who experienced an AE representing an immunologic etiology and considered to be causally related to drug exposure	Up to approximately 41 months
Number of Participants Who Experienced an Hepatic Event of Clinical Interest (HECI)	Number of participants who experienced a hepatic ECI not due to disease progression as judged by the investigator.	Up to approximately 41 months
Number of Participants Who Discontinued Study Drug Due to an Adverse Event	Number of participants who discontinued study treatment due to an AE	Up to approximately 41 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

General Publications

• Llovet JM, Kudo M, Merle P, Meyer T, Qin S, Ikeda M, Xu R, Edeline J, Ryoo BY, Ren Z, Masi G, Kwiatkowski M, Lim HY, Kim JH, Breder V, Kumada H, Cheng AL, Galle PR, Kaneko S, Wang A, Mody K, Dutcus C, Dubrovsky L, Siegel AB, Finn RS; LEAP-002 Investigators. Lenvatinib plus pembrolizumab versus lenvatinib plus placebo for advanced hepatocellular carcinoma (LEAP-002): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2023 Dec;24(12):1399-1410. doi: 10.1016/S1470-2045(23)00469-2.

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): December 31, 2018
• Primary Completion (Actual): June 21, 2022
• Study Completion (Estimated): August 29, 2024

Study Registration Dates

• First Submitted: October 18, 2018
• First Submitted That Met QC Criteria: October 18, 2018
• First Posted (Actual): October 22, 2018

Study Record Updates

• Last Update Posted (Actual): January 10, 2024
• Last Update Submitted That Met QC Criteria: January 5, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: receptor tyrosine kinase inhibitor; 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: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Immune Checkpoint Inhibitors; Pembrolizumab; Lenvatinib
• Other Study ID Numbers: 7902-002; MK-7902-002 (Other Identifier: Merck Protocol Number); E7080-G000-311 (Other Identifier: Eisai Protocol Number); LEAP-002 (Other Identifier: Merck); 194590 (Registry Identifier: JAPIC-CTI); 2018-002983-26 (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