Safety and Efficacy of Lenvatinib (E7080/MK-7902) With Pembrolizumab (MK-3475) in Combination With Transarterial Chemoembolization (TACE) in Participants With Incurable/Non-metastatic Hepatocellular Carcinoma (MK-7902-012/E7080-G000-318/LEAP-012)

A Phase 3 Multicenter, Randomized, Double-blinded, Active-controlled, Clinical Study to Evaluate the Safety and Efficacy of Lenvatinib (E7080/MK-7902) With Pembrolizumab (MK-3475) in Combination With Transarterial Chemoembolization (TACE) Versus TACE in Participants With Incurable/Non-metastatic Hepatocellular Carcinoma (LEAP-012)

The purpose of this study is to evaluate the efficacy and safety of lenvatinib and pembrolizumab in combination with TACE versus TACE plus oral and intravenous (IV) placebos in participants with incurable, non-metastatic hepatocellular carcinoma (HCC). The primary hypotheses are that pembrolizumab plus lenvatinib in combination with TACE is superior to placebo plus TACE with respect to progression-free survival (PFS) and overall survival (OS).

Study Overview

• Status: Completed
• Conditions: Carcinoma, Hepatocellular
• Intervention / Treatment: Drug: Lenvatinib; Biological: Pembrolizumab; Procedure: TACE; Drug: Oral Placebo; Drug: IV Placebo

• Study Type: Interventional
• Enrollment (Actual): 479
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • St George Hospital ( Site 0005)
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital-Gastroenterology & Hepatology ( Site 0009)
  • Queensland
    • Brisbane, Queensland, Australia, 4102
      • Princess Alexandra Hospital ( Site 0006)
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Austin Health ( Site 0008)
    • Melbourne, Victoria, Australia, 3004
      • Alfred Health ( Site 0004)
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital ( Site 0002)
• Brazil
  • São Paulo, Brazil, 01509-900
    • A.C. Camargo Cancer Center ( Site 0054)
  • Rio Grande do Norte
    • Natal, Rio Grande do Norte, Brazil, 59075-740
      • Liga Norte Riograndense Contra o Câncer-Centro de Pesquisa Clínica ( Site 0057)
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 91350-200
      • Hospital Nossa Senhora da Conceição-Centro Integrado de Pesquisa em Oncologia ( Site 0056)
  • Santa Catarina
    • Blumenau, Santa Catarina, Brazil, 89010-340
      • Clinica de Oncologia Reichow ( Site 0052)
  • São Paulo
    • Barretos, São Paulo, Brazil, 14784-400
      • Fundação Pio XII - Hospital de Câncer de Barretos-Unidade de Pesquisa Clínica ( Site 0058)
    • Jaú, São Paulo, Brazil, 17210-120
      • Fundacao Dr Amaral Carvalho ( Site 0050)
    • São José do Rio Preto, São Paulo, Brazil, 15090-000
      • Hospital de Base de Sao Jose de Rio Preto ( Site 0043)
    • São Paulo, São Paulo, Brazil, 01323-001
      • BP - A Beneficencia Portuguesa de São Paulo ( Site 0046)
• Chile
  • Araucania
    • Temuco, Araucania, Chile, 4800827
      • Centro Investigación del Cáncer James Lind ( Site 0064)
  • Region M. de Santiago
    • Santiago, Region M. de Santiago, Chile, 7560908
      • Centro de Oncología de Precisión-Oncology ( Site 0068)
    • Santiago, Region M. de Santiago, Chile, 8330024
      • Centro de Cancer Nuestra Senora de la Esperanza ( Site 0065)
    • Santiago, Region M. de Santiago, Chile, 8420383
      • Bradfordhill ( Site 0066)
• China
  • Anhui
    • Heifei, Anhui, China, 230001
      • Anhui Provincial Hospital ( Site 0092)
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer Hospital ( Site 0099)
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer Hospital ( Site 0105)
    • Beijing, Beijing Municipality, China, 100730
      • Peking Union Medical College Hospital ( Site 0087)
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400042
      • Chinese People s Liberation Army Army Characteristic Medical Center ( Site 0117)
    • Chongqing, Chongqing Municipality, China, 404000
      • Chongqing University Three Gorges Hospital ( Site 0859)
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Provincial Cancer Hospital ( Site 0085)
    • Fuzhou, Fujian, China, 350014
      • The First Affiliated Hospital of Fujian Medical University ( Site 0089)
    • Fuzhou, Fujian, China, 350008
      • Mengchao Hepatobiliary Hospital of Fujian Medical University ( Site 0121)
    • Xiamen, Fujian, China, 361015
      • Zhongshan Hospital Fudan University (Xiamen Branch) ( Site 0133)
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Zhujiang Hospital of Southern Medical University ( Site 0115)
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Provincial People s Hospital ( Site 0100)
    • Guangzhou, Guangdong, China, 510515
      • NANFANG HOSPITAL SOUTHERN MEDICAL UNIVERSITY ( Site 0088)
    • Guangzhou, Guangdong, China, 510700
      • SUN YAT-SEN UNIVERSITY CANCER CENTRE ( Site 0128)
    • Zhuhai, Guangdong, China, 519000
      • Jinan University - Zhuhai People's Hospital-Intervention Department ( Site 0856)
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Guangxi Medical University Affiliated Tumor Hospital-Hepatological surgery ( Site 0862)
  • Hainan
    • Haikou, Hainan, China, 570311
      • Hainan General Hospital ( Site 0112)
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Harbin Medical University Cancer Hospital ( Site 0090)
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital ( Site 0114)
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital ( Site 0101)
    • Wuhan, Hubei, China, 430000
      • Tongji Hospital Tongji Medical,Science & Technology ( Site 0126)
  • Hunan
    • Changsha, Hunan, China, 410005
      • Hunan Provincial People's Hospital ( Site 0113)
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital ( Site 0096)
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • The First Affiliated Hospital of Soochow University ( Site 0120)
  • Jiangxi
    • Nanchang, Jiangxi, China, 330029
      • Jiangxi Provincial Cancer Hospital-Cancer Hospital ( Site 0134)
  • Shaanxi
    • Xi'an, Shaanxi, China, 710100
      • Xi'an International Medical Center Hospital ( Site 0860)
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200028
      • The Third Affiliated Hospital of the PLA Navy Medical University ( Site 0123)
    • Shanghai, Shanghai Municipality, China, 200032
      • Fudan University Shanghai Cancer Center ( Site 0106)
    • Shanghai, Shanghai Municipality, China, 200032
      • Zhongshan Hospital Fudan University ( Site 0084)
  • Shanxi
    • Xi’an, Shanxi, China, 710048
      • The First Affiliated Hospital of Xi an Jiaotong University ( Site 0108)
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital of Sichuan University ( Site 0119)
    • Suining, Sichuan, China, 629000
      • Suining Central Hospital ( Site 0857)
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300060
      • Tianjin Medical University Cancer Institute & Hospital ( Site 0098)
    • Tianjin, Tianjin Municipality, China, 300170
      • Tianjin Third Central Hospital ( Site 0861)
  • Yunnan
    • Kunming, Yunnan, China, 650200
      • The First Hospital of Kunming ( Site 0124)
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • 2nd Affil Hosp of Zhejiang University College of Medicine ( Site 0110)
    • Hangzhou, Zhejiang, China, 310018
      • Sir Run Run Shaw Hospital ( Site 0094)
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital ( Site 0103)
    • Ningbo, Zhejiang, China, 315048
      • Ningbo Medical Center LiHuili Hospital ( Site 0132)
• Colombia
  • Antioquia
    • Medellín, Antioquia, Colombia, 050034
      • Hospital Pablo Tobon Uribe ( Site 0145)
  • Bogota D.C.
    • Bogotá, Bogota D.C., Colombia, 110221
      • Administradora Country S.A. ( Site 0137)
  • Santander Department
    • Piedecuesta, Santander Department, Colombia, 681017
      • Fundacion Cardiovascular de Colombia ( Site 0136)
  • Valle del Cauca Department
    • Cali, Valle del Cauca Department, Colombia, 760032
      • Fundación Valle del Lili ( Site 0140)
• Denmark
  • Capital Region
    • Herlev, Capital Region, Denmark, 2730
      • Herlev Hospital ( Site 0170)
  • Central Jutland
    • Aarhus N, Central Jutland, Denmark, 8200
      • Aarhus Universitets hospital ( Site 0175)
  • Region Syddanmark
    • Odense, Region Syddanmark, Denmark, 5000
      • Odense Universitetshospital ( Site 0160)
• France
  • Auvergne
    • Lyon, Auvergne, France, 69004
      • Hopital de la Croix-Rousse ( Site 0193)
  • Bouches-du-Rhone
    • Marseille, Bouches-du-Rhone, France, 13005
      • Hopital de la Timone ( Site 0188)
  • Gironde
    • Pessac, Gironde, France, 33604
      • CHU Bordeaux Haut-Leveque ( Site 0185)
  • Meurthe-et-Moselle
    • Vandœuvre-lès-Nancy, Meurthe-et-Moselle, France, 54500
      • C.H.U. de Nancy. Hopital de Brabois Adultes ( Site 0180)
  • Val-de-Marne
    • Créteil, Val-de-Marne, France, 94000
      • A.P.H. Paris, Hopital Henri Mondor ( Site 0179)
    • Villejuif, Val-de-Marne, France, 94800
      • Hopital Paul Brousse ( Site 0182)
• Germany
  • Berlin, Germany, 13353
    • Charite - Universitaetsmedizin ( Site 0204)
  • Hamburg, Germany, 20246
    • Universitaetsklinikum Hamburg-Eppendorf ( Site 0207)
  • Baden-Wurttemberg
    • Freiburg im Breisgau, Baden-Wurttemberg, Germany, 79106
      • Universitaetsklinikum Freiburg ( Site 0199)
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60488
      • Krankenhaus Nord-West GmbH ( Site 0208)
  • Lower Saxony
    • Hanover, Lower Saxony, Germany, 30625
      • Medizinische Hochschule Hannover ( Site 0200)
  • North Rhine-Westphalia
    • Bonn, North Rhine-Westphalia, Germany, 53127
      • Universitaetsklinikum Bonn ( Site 0203)
  • Saxony
    • Leipzig, Saxony, Germany, 04103
      • Universitaetsklinikum Leipzig ( Site 0202)
  • Saxony-Anhalt
    • Halle, Saxony-Anhalt, Germany, 06120
      • Universitaetsklinikum Halle ( Site 0213)
  • Schleswig-Holstein
    • Lübeck, Schleswig-Holstein, Germany, 23538
      • Universitaetsklinikum Schleswig-Holstein-Campus Lubeck ( Site 0215)
• Hong Kong
  • Shatin, Hong Kong
    • Prince of Wales Hospital ( Site 0242)
• Hungary
  • Budapest, Hungary, 1085
    • Semmelweis University ( Site 0264)
  • Somogy County
    • Kaposvár, Somogy County, Hungary, 7400
      • Somogy Megyei Kaposi Mór Oktató Kórház-Oncology center ( Site 0267)
  • Zala County
    • Zalaegerszeg, Zala County, Hungary, 8900
      • Zala Megyei Szent Rafael Korhaz ( Site 0265)
• Ireland
  • Dublin, Ireland, D04 T6F4
    • St Vincents University Hospital ( Site 0690)
• Israel
  • Afula, Israel, 1834111
    • Emek Medical Center ( Site 0307)
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus-Oncology Division ( Site 0305)
  • Jerusaelm, Israel, 9112001
    • Hadassah Ein Karem Jerusalem ( Site 0303)
  • Petah Tikva, Israel, 4941 492
    • Rabin Medical Center ( Site 0304)
  • Tel Aviv, Israel, 6423906
    • Sourasky Medical Center ( Site 0306)
• Italy
  • Brescia, Italy, 25123
    • Azienda Ospedaliera Spedali Civili di Brescia-Oncology ( Site 0334)
  • Milan, Italy, 20122
    • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico ( Site 0325)
  • Naples, Italy, 80131
    • Az Osp di Rilievo Nazionale A. Cardarelli ( Site 0329)
  • Ravenna, Italy, 48121
    • Azienda USL della Romagna-Dipartimento di Oncologia ed Ematologia ( Site 0332)
  • Roma, Italy, 00168
    • Policlinico Universitario -Agostino Gemelli ( Site 0328)
  • Campania
    • Naples, Campania, Italy, 80147
      • Ospedale del Mare ( Site 0327)
  • Milano
    • Milan, Milano, Italy, 20162
      • ASST Grande Ospedale Metropolitano Niguarda-Oncologia Falck ( Site 0331)
  • Piedmont
    • Turin, Piedmont, Italy, 10128
      • Ospedale Mauriziano-SCDU ONCOLOGIA MEDICA ( Site 0333)
  • Sicily
    • Messina, Sicily, Italy, 98124
      • AOU Policlinico G. Martino ( Site 0324)
• Japan
  • Chiba, Japan, 260-8677
    • Chiba University Hospital ( Site 0346)
  • Fukuoka, Japan, 8108563
    • National Hospital Organization Kyushu Medical Center ( Site 0361)
  • Hiroshima, Japan, 734-8551
    • Hiroshima University Hospital ( Site 0360)
  • Kumamoto, Japan, 860-8556
    • Kumamoto University Hospital ( Site 0372)
  • Kyoto, Japan, 602-8566
    • University Hospital,Kyoto Prefectural University of Medicine ( Site 0367)
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute ( Site 0357)
  • Osaka, Japan, 543-8555
    • Japanese Red Cross Osaka Hospital ( Site 0356)
  • Saga, Japan, 840-8571
    • Saga-Ken Medical Centre Koseikan ( Site 0363)
  • Tokyo, Japan, 105-8470
    • Toranomon Hospital ( Site 0349)
  • Tokyo, Japan, 113-0033
    • Juntendo University Hospital ( Site 0371)
  • Tokyo, Japan, 113-8655
    • The University of Tokyo Hospital ( Site 0348)
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East ( Site 0347)
  • Ehime
    • Tōon, Ehime, Japan, 791-0295
      • Ehime University Hospital ( Site 0368)
  • Fukuoka
    • Kurume, Fukuoka, Japan, 830-0011
      • Kurume University Hospital ( Site 0362)
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-0033
      • Sapporo Kosei General Hospital ( Site 0345)
  • Ishikawa-ken
    • Kanazawa, Ishikawa-ken, Japan, 920-8641
      • Kanazawa University Hospital ( Site 0354)
  • Kagawa-ken
    • Takamatsu, Kagawa-ken, Japan, 760-8557
      • Kagawa Prefectural Central Hospital ( Site 0364)
  • Kanagawa
    • Kawasaki, Kanagawa, Japan, 213-8587
      • Toranomon Hospital Kajigaya ( Site 0369)
    • Yokohama, Kanagawa, Japan, 232-0024
      • Yokohama City University Medical Center ( Site 0351)
    • Yokohama, Kanagawa, Japan, 241-8515
      • Kanagawa Cancer Center ( Site 0352)
  • Nara
    • Kashihara, Nara, Japan, 634-8522
      • Nara Medical University Hospital ( Site 0359)
  • Osaka
    • Sayama, Osaka, Japan, 589-8511
      • Kindai University Hospital ( Site 0358)
  • Saitama
    • Iruma-gun, Saitama, Japan, 350-0495
      • Saitama Medical University Hospital ( Site 0370)
  • Shizuoka
    • Suntogun, Shizuoka, Japan, 411-8777
      • Shizuoka Cancer Center ( Site 0365)
  • Tochigi
    • Shimotsuke, Tochigi, Japan, 329-0498
      • Jichi Medical University Hospital ( Site 0353)
• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • Universitair Medisch Centrum Utrecht-Medical Oncology ( Site 0441)
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229 HX
      • Maastricht University Medical Centre ( Site 0440)
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1105 AZ
      • AMC ( Site 0438)
  • South Holland
    • Leiden, South Holland, Netherlands, 2333 ZA
      • Leids Universitair Medisch Centrum-Medical Oncology ( Site 0442)
    • Rotterdam, South Holland, Netherlands, 3015 GD
      • Erasmus University Medical Center ( Site 0439)
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital ( Site 0459)
• Norway
  • Oslo, Norway, 0450
    • Oslo Universitetssykehus Ullevål ( Site 0500)
• Portugal
  • Coimbra, Portugal, 3000-075
    • Centro Hospitalar e Universitario de Coimbra ( Site 0502)
  • Lisbon, Portugal, 1169-050
    • Unidade Local de Saude de São José - Hospital de Santo Antonio dos Capuchos ( Site 0505)
  • Porto, Portugal, 4099-001
    • Centro Hospitalar do Porto, E.P.E. - Hospital Geral de Sto. Antonio ( Site 0504)
  • Porto, Portugal, 4200-072
    • Inst. Portugues de Oncologia de Porto Francisco Gentil EPE ( Site 0503)
  • Porto, Portugal, 4200-319
    • Centro Hospitalar de Sao Joao. EPE - Hospital de Sao Joao ( Site 0501)
• Puerto Rico
  • Hato Rey, Puerto Rico, 00917
    • Puerto Rico Medical Research Center LLC ( Site 0523)
  • Ponce, Puerto Rico, 00717
    • Ad-Vance Medical Research LLC ( Site 0527)
  • San Juan, Puerto Rico, 00921-3201
    • VA Caribbean Healthcare System ( Site 0524)
  • San Juan, Puerto Rico, 00927
    • FDI Clinical Research ( Site 0522)
• South Korea
  • Seoul, South Korea, 03080
    • Seoul National University Hospital ( Site 0567)
  • Seoul, South Korea, 03722
    • Severance Hospital Yonsei University Health System ( Site 0564)
  • Seoul, South Korea, 05505
    • Asan Medical Center ( Site 0565)
  • Seoul, South Korea, 06351
    • Samsung Medical Center ( Site 0566)
  • Seoul, South Korea, 06591
    • The Catholic University of Korea St. Mary s Hospital ( Site 0571)
  • Seoul, South Korea, 08308
    • Korea University Guro Hospital ( Site 0573)
  • Jeonranamdo
    • Hwasun, Jeonranamdo, South Korea, 58128
      • Chonnam National University Hwasun Hospital ( Site 0572)
  • Kyonggi-do
    • Seongnam-si, Kyonggi-do, South Korea, 13620
      • Seoul National University Bundang Hospital ( Site 0570)
  • Pusan-Kwangyokshi
    • Busan, Pusan-Kwangyokshi, South Korea, 49241
      • Pusan National University Hospital ( Site 0568)
  • Taegu-Kwangyokshi
    • Daegu, Taegu-Kwangyokshi, South Korea, 41944
      • Kyungpook National University Hospital ( Site 0569)
• Spain
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon ( Site 0598)
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal ( Site 0593)
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos ( Site 0597)
  • Seville, Spain, 41013
    • Hospital Virgen del Rocio ( Site 0591)
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro ( Site 0596)
  • Valenciana, Comunitat
    • Valencia, Valenciana, Comunitat, Spain, 46014
      • Hospital General Universitario de Valencia ( Site 0595)
• Taiwan
  • Kaohsiung City, Taiwan, 807
    • Kaohsiung Medical University Hospital ( Site 0611)
  • Taichung, Taiwan, 40447
    • China Medical University Hospital-Surgical Department ( Site 0610)
  • Taichung, Taiwan, 407
    • Taichung Veterans General Hospital ( Site 0613)
  • Tainan, Taiwan, 70457
    • National Cheng Kung University Hospital ( Site 0608)
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital ( Site 0606)
  • Taipei, Taiwan, 112201
    • Taipei Veterans General Hospital-Division of Gastroenterology & Hepatology, Department of Medicine ( Site 0612)
  • Taoyuan, Taiwan, 333
    • Chang Gung Medical Foundation. Linkou ( Site 0607)
  • Kaohsiung
    • Kaohsiung City, Kaohsiung, Taiwan, 833
      • Chang Gung Medical Foundation. Kaohsiung Branch ( Site 0609)
• Thailand
  • Bangkok
    • Bangkok, Bangkok, Thailand, 10330
      • Chulalongkorn University ( Site 0627)
    • Bangkok, Bangkok, Thailand, 10400
      • Ramathibodi Hospital, Mahidol University ( Site 0628)
    • Bangkok, Bangkok, Thailand, 10700
      • Faculty of Medicine Siriraj Hospital ( Site 0629)
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06230
    • Hacettepe University Medical Faculty ( Site 0653)
  • Ankara, Turkey (Türkiye), 06800
    • Ankara City Hospital-Medical Oncology ( Site 0661)
  • Edirne, Turkey (Türkiye), 22030
    • Trakya University Medical Faculty Balkan Oncology Hospital ( Site 0648)
  • Istanbul, Turkey (Türkiye), 34093
    • Bezmialem Vakf Üniversitesi-Oncology ( Site 0660)
  • Izmir, Turkey (Türkiye), 35100
    • Ege University Medical Faculty Tulay Aktas Oncology Hospital ( Site 0654)
  • Izmir, Turkey (Türkiye), 35575
    • I.E.U. Medical Point Hastanesi ( Site 0649)
  • Konya, Turkey (Türkiye), 42080
    • Konya Necmettin Erbakan University Medical Faculty ( Site 0652)
  • Malatya, Turkey (Türkiye), 44280
    • Inonu Universitesi Medical Fakultesi ( Site 0650)
• Ukraine
  • Kharkivs’ka Oblast’
    • Kharkiv, Kharkivs’ka Oblast’, Ukraine, 61070
      • Communal non profit enterprise Regional Clinical Oncology Center ( Site 0669)
• United Kingdom
  • London, City of
    • London, London, City of, United Kingdom, EC1A 7BE
      • Barts Health NHS Trust ( Site 0692)
    • London, London, City of, United Kingdom, SW3 6JJ
      • Royal Marsden NHS Foundation Trust ( Site 0694)
    • Sutton, London, City of, United Kingdom, SM2 5PT
      • Royal Marsden NHS Trust ( Site 0693)
• United States
  • Arizona
    • Tucson, Arizona, United States, 85711
      • Arizona Oncology Associates PC- HOPE ( Site 0770)
  • California
    • La Jolla, California, United States, 92037
      • Scripps Clinic Torrey Pines ( Site 0714)
    • Los Angeles, California, United States, 90033
      • USC Norris Comprehensive Cancer Center ( Site 0717)
    • Los Angeles, California, United States, 90404
      • UCLA Hematology/Oncology - Santa Monica ( Site 0720)
    • Orange, California, United States, 92868
      • UC Irvine Health ( Site 0718)
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale Cancer Center ( Site 0724)
  • Florida
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital ( Site 0764)
  • Idaho
    • Boise, Idaho, United States, 83712
      • Mountain States Tumor Institute ( Site 0773)
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospital and Clinics ( Site 0729)
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Cancer Center ( Site 0731)
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville ( Site 0757)
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane Medical Center ( Site 0787)
    • New Orleans, Louisiana, United States, 70112
      • University Medical Center New Orleans ( Site 0733)
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital-GI/Hepatology Research ( Site 0735)
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Saint Louis University ( Site 0769)
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Comprehensive Cancer Center ( Site 0805)
  • New York
    • Lake Success, New York, United States, 11042
      • Monter Cancer Center ( Site 0780)
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai ( Site 0744)
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health ( Site 0741)
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center ( Site 0791)
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center ( Site 0759)
    • Sylvania, Ohio, United States, 43560
      • ProMedica Flower Hospital ( Site 0796)
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Stephenson Cancer Center ( Site 0745)
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU Center for Health & Healing ( Site 0746)
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Hershey Medical Center ( Site 0766)
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Research Institute ( Site 0784)
  • West Virginia
    • Huntington, West Virginia, United States, 25701
      • Edwards Comprehensive Cancer Center ( Site 0786)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Has a diagnosis of HCC confirmed by radiology, histology, or cytology
• Has HCC localized to the liver and not amenable to curative treatment
• Participants with Hepatitis C virus (HCV) are eligible if treatment was completed at least 1 month prior to starting study intervention
• Participants with Hepatitis B virus (HBV) are eligible
• Has adequately controlled blood pressure with or without antihypertensive medications
• Has adequate organ function

Exclusion Criteria:

• Is currently a candidate for liver transplantation
• Has had gastric bleeding within the last 6 months
• Has ascites that is not controlled with medication
• Has significant cardiovascular impairment within 12 months of the first dose of study intervention such as congestive heart failure
• Has a serious nonhealing wound, ulcer, or bone fracture
• Has received locoregional therapy to existing liver lesions

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: Lenvatinib plus Pembrolizumab plus TACE; Participants will receive a combination of lenvatinib, pembrolizumab, and TACE. Lenvatinib will be administered at a dose of 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 during each 21-day cycle until progressive disease or unacceptable toxicity (up to 2 years [~35 cycles] or longer with Sponsor approval). Pembrolizumab will be administered via IV infusion at a dose of 400 mg once every 6 weeks (Q6W) for up to 2 years (~17 doses). Participants will undergo TACE as a background procedure of chemotherapeutic and embolic agent(s).	Drug: Lenvatinib; Administered at a dose of 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) via oral capsules once a day during each 21-day cycle.; Other Names: E7080; MK-7902; LENVIMA®; Biological: Pembrolizumab; Administered via IV infusion at a dose of 400 mg once every 6 weeks (Q6W).; Other Names: MK-3475; KEYTRUDA®; Procedure: TACE; Conducted as a background procedure of chemotherapeutic and embolic agent(s).
Active Comparator: Oral Placebo plus IV Placebo plus TACE; Participants will receive a combination of lenvatinib-matching oral placebo, pembrolizumab-matching IV placebo, and TACE. Lenvatinib-matching oral placebo will be administered once a day during each 21-day cycle for up to 2 years (~35 cycles) or longer with Sponsor approval and pembrolizumab-matching IV placebo will be administered once every 6 weeks (Q6W) for up to 2 years (~17 doses). Participants will undergo TACE as a background procedure of chemotherapeutic and embolic agent(s).	Procedure: TACE; Conducted as a background procedure of chemotherapeutic and embolic agent(s).; Drug: Oral Placebo; Lenvatinib-matching placebo administered via oral capsules once a day during each 21-day cycle.; Drug: IV Placebo; Pembrolizumab-matching placebo administered via IV infusion once every 6 weeks (Q6W).

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 is defined as the time from randomization to the first documented progressive disease or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 as assessed by blinded independent central review (BICR).	Up to ~43 months
Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to ~95 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)	PFS is defined as the time from randomization to the first documented progressive disease or death due to any cause, whichever occurs first. Responses are according to mRECIST as assessed by BICR.	Up to ~43 months
Objective Response Rate (ORR) per mRECIST	ORR is 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). Responses are according to mRECIST as assessed by BICR.	Up to ~95 months
Disease Control Rate (DCR) per mRECIST	DCR is defined as the percentage of participants who have a best overall response of CR (disappearance of any intratumoral arterial enhancement in all target lesions), 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), or stable disease (SD). Responses are according to mRECIST as assessed by BICR.	Up to ~95 months
Duration of Response (DOR) per mRECIST	DOR is determined by disease assessment and is defined as the time from the first documented evidence of a response of CR (disappearance of any intratumoral arterial enhancement in all target lesions) or 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) until the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to mRECIST as assessed by BICR.	Up to ~95 months
Time to Progression (TTP) per mRECIST	TTP is defined as the time from randomization to the first documented disease progression. Responses are according to mRECIST as assessed by BICR.	Up to ~95 months
Percentage of Participants Who Experience At Least One Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience at least one AE will be reported.	Up to ~95 months
Percentage of Participants Who Experience At Least One Serious Adverse Event (SAE)	An SAE is an AE that results in death, is life threatening, requires or prolongs a hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is a cancer, is associated with an overdose, or is another important medical event. The percentage of participants who experience at least one SAE will be reported.	Up to ~95 months
Percentage of Participants Who Experience At Least One Hepatic Event of Clinical Interest (ECI)	Percentage of participants with Hepatic ECIs not due to disease progression or TACE as assessed by the investigator will be reported.	Up to ~95 months
Percentage of Participants Who Discontinue Study Drug Due to an AE	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study drug due to an AE will be reported.	Up to ~95 months
ORR per RESCIST 1.1	ORR is 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 of diameters). Responses are according to RECIST 1.1 as assessed by BICR.	Up to ~95 months
DCR per RECIST 1.1	DCR is defined as the percentage of participants who have a best overall response of CR (disappearance of all target lesions), PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters), or SD. Responses are according to RECIST 1.1 as assessed by BICR.	Up to ~95 months
DOR per RECIST 1.1	DOR is determined by disease assessment and is defined as the time from the first documented evidence of a response of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) until the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 as assessed by BICR.	Up to ~95 months
TTP per RECIST 1.1	TTP is defined as the time from randomization to the first documented disease progression. Responses are according to RECIST 1.1 as assessed by BICR.	Up to ~95 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

• Verset G, Borbath I, Karwal M, Verslype C, Van Vlierberghe H, Kardosh A, Zagonel V, Stal P, Sarker D, Palmer DH, Vogel A, Edeline J, Cattan S, Kudo M, Cheng AL, Ogasawara S, Daniele B, Chan SL, Knox JJ, Qin S, Siegel AB, Chisamore M, Hatogai K, Wang A, Finn RS, Zhu AX. Pembrolizumab Monotherapy for Previously Untreated Advanced Hepatocellular Carcinoma: Data from the Open-Label, Phase II KEYNOTE-224 Trial. Clin Cancer Res. 2022 Jun 13;28(12):2547-2554. doi: 10.1158/1078-0432.CCR-21-3807.
• Taylor MH, Schmidt EV, Dutcus C, Pinheiro EM, Funahashi Y, Lubiniecki G, Rasco D. The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. Future Oncol. 2021 Feb;17(6):637-648. doi: 10.2217/fon-2020-0937. Epub 2020 Dec 10.
• Kloeckner R, Galle PR, Bruix J. Local and Regional Therapies for Hepatocellular Carcinoma. Hepatology. 2021 Jan;73 Suppl 1:137-149. doi: 10.1002/hep.31424. Epub 2020 Nov 6. No abstract available.
• Llovet JM, Vogel A, Madoff DC, Finn RS, Ogasawara S, Ren Z, Mody K, Li JJ, Siegel AB, Dubrovsky L, Kudo M. Randomized Phase 3 LEAP-012 Study: Transarterial Chemoembolization With or Without Lenvatinib Plus Pembrolizumab for Intermediate-Stage Hepatocellular Carcinoma Not Amenable to Curative Treatment. Cardiovasc Intervent Radiol. 2022 Apr;45(4):405-412. doi: 10.1007/s00270-021-03031-9. Epub 2022 Feb 4.
• Kudo M, Ren Z, Guo Y, Han G, Lin H, Zheng J, Ogasawara S, Kim JH, Zhao H, Li C, Madoff DC, Ghobrial RM, Kawaoka T, Gerolami R, Ikeda M, Kumada H, El-Khoueiry AB, Vogel A, Peng X, Mody K, Dutcus C, Dubrovsky L, Siegel AB, Finn RS, Llovet JM; LEAP-012 investigators. Transarterial chemoembolisation combined with lenvatinib plus pembrolizumab versus dual placebo for unresectable, non-metastatic hepatocellular carcinoma (LEAP-012): a multicentre, randomised, double-blind, phase 3 study. Lancet. 2025 Jan 18;405(10474):203-215. doi: 10.1016/S0140-6736(24)02575-3. Epub 2025 Jan 8.

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2020
• Primary Completion (Actual): August 19, 2025
• Study Completion (Actual): March 26, 2026

Study Registration Dates

• First Submitted: January 27, 2020
• First Submitted That Met QC Criteria: January 27, 2020
• First Posted (Actual): January 29, 2020

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

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)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Parkinson Disease 4, Autosomal Dominant Lewy Body; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; pembrolizumab; lenvatinib
• Other Study ID Numbers: 7902-012; MK-7902-012 (Other Identifier: MSD Protocol Number); LEAP-012 (Other Identifier: MSD); E7080-G000-318 (Other Identifier: Eisai Protocol Number); 205286 (Registry Identifier: JAPIC-CTI); 2019-002345-37 (EudraCT Number); 2022-502116-36-00 (Registry Identifier: EU CT); U1111-1283-3439 (Registry Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/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