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)
Carcinoma, Hepatocellular
About this trial
This is an interventional treatment trial for Carcinoma, Hepatocellular focused on measuring receptor tyrosine kinase inhibitor, programmed cell death 1 (PD-1, PD1), programmed cell death ligand 1 (PD-L1, PDL1)
Eligibility Criteria
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
Sites / Locations
- Arizona Oncology Associates PC- HOPE ( Site 0770)
- Scripps Clinic Torrey Pines ( Site 0714)
- USC Norris Comprehensive Cancer Center ( Site 0717)
- UCLA Hematology/Oncology - Santa Monica ( Site 0720)
- UC Irvine Health ( Site 0718)
- Yale Cancer Center ( Site 0724)
- Tampa General Hospital ( Site 0764)
- Mountain States Tumor Institute ( Site 0773)
- University of Iowa Hospital and Clinics ( Site 0729)
- University of Kansas Cancer Center ( Site 0731)
- University of Louisville ( Site 0757)
- Tulane Medical Center ( Site 0787)
- University Medical Center New Orleans ( Site 0733)
- Henry Ford Hospital-GI/Hepatology Research ( Site 0735)
- Saint Louis University ( Site 0769)
- University of New Mexico Comprehensive Cancer Center ( Site 0805)
- Monter Cancer Center ( Site 0780)
- Icahn School of Medicine at Mount Sinai ( Site 0744)
- Wake Forest Baptist Health ( Site 0741)
- University of Cincinnati Medical Center ( Site 0791)
- The Ohio State University Wexner Medical Center ( Site 0759)
- ProMedica Flower Hospital ( Site 0796)
- Stephenson Cancer Center ( Site 0745)
- OHSU Center for Health & Healing ( Site 0746)
- Penn State Hershey Medical Center ( Site 0766)
- Houston Methodist Research Institute ( Site 0784)
- Edwards Comprehensive Cancer Center ( Site 0786)
- St George Hospital ( Site 0005)
- Westmead Hospital-Gastroenterology & Hepatology ( Site 0009)
- Princess Alexandra Hospital ( Site 0006)
- Austin Health ( Site 0008)
- Alfred Health ( Site 0004)
- Royal Perth Hospital ( Site 0002)
- Liga Norte Riograndense Contra o Câncer-Centro de Pesquisa Clínica ( Site 0057)
- Hospital Nossa Senhora da Conceição-Centro Integrado de Pesquisa em Oncologia ( Site 0056)
- Clinica de Oncologia Reichow ( Site 0052)
- Fundação Pio XII - Hospital de Câncer de Barretos-Unidade de Pesquisa Clínica ( Site 0058)
- Fundacao Dr Amaral Carvalho ( Site 0050)
- Hospital de Base de Sao Jose de Rio Preto ( Site 0043)
- BP - A Beneficencia Portuguesa de São Paulo ( Site 0046)
- A.C. Camargo Cancer Center ( Site 0054)
- Centro Investigación del Cáncer James Lind ( Site 0064)
- Centro de Oncología de Precisión-Oncology ( Site 0068)
- Centro de Cancer Nuestra Senora de la Esperanza ( Site 0065)
- Bradfordhill ( Site 0066)
- Anhui Provincial Hospital ( Site 0092)
- Beijing Cancer Hospital ( Site 0099)
- Beijing Cancer Hospital ( Site 0105)
- Peking Union Medical College Hospital ( Site 0087)
- Chinese People s Liberation Army Army Characteristic Medical Center ( Site 0117)
- Chongqing Three Gorges Central Hospital ( Site 0859)
- Mengchao Hepatobiliary Hospital of Fujian Medical University ( Site 0121)
- Fujian Provincial Cancer Hospital ( Site 0085)
- The First Affiliated Hospital of Fujian Medical University ( Site 0089)
- Zhongshan Hospital Fudan University (Xiamen Branch) ( Site 0133)
- Zhujiang Hospital of Southern Medical University ( Site 0115)
- Guangdong Provincial People s Hospital ( Site 0100)
- Nanfang Hospital of Southern Medical University ( Site 0088)
- SUN YAT-SEN UNIVERSITY CANCER CENTRE-Department of Medical Imaging and Interventional Radiology ( Si
- Jinan University - Zhuhai People's Hospital-Intervention Department ( Site 0856)
- Guangxi Medical University Affiliated Tumor Hospital-Hepatological surgery ( Site 0862)
- Hainan General Hospital ( Site 0112)
- Harbin Medical University Cancer Hospital ( Site 0090)
- Henan Cancer Hospital ( Site 0114)
- Tongji Hospital Tongji Medical,Science & Technology ( Site 0126)
- Hubei Cancer Hospital ( Site 0101)
- Hunan Provincial People's Hospital ( Site 0113)
- Hunan Cancer Hospital ( Site 0096)
- The First Affiliated Hospital of Soochow University ( Site 0120)
- Jiangxi Provincial Cancer Hospital-Cancer Hospital ( Site 0134)
- Xi'an International Medical Center Hospital ( Site 0860)
- The Third Affiliated Hospital of Naval Medical University ( Site 0123)
- Fudan University Shanghai Cancer Center ( Site 0106)
- Zhongshan Hospital Fudan University ( Site 0084)
- The First Affiliated Hospital of Xi an Jiaotong University ( Site 0108)
- West China Hospital of Sichuan University ( Site 0119)
- Suining Central Hospital ( Site 0857)
- Tianjin Medical University Cancer Institute & Hospital ( Site 0098)
- Tianjin Third Central Hospital ( Site 0861)
- The First Hospital of Kunming ( Site 0124)
- 2nd Affil Hosp of Zhejiang University College of Medicine ( Site 0110)
- Sir Run Run Shaw Hospital ( Site 0094)
- Zhejiang Cancer Hospital ( Site 0103)
- Ningbo Medical Center ( Site 0132)
- Hospital Pablo Tobon Uribe ( Site 0145)
- Administradora Country S.A. ( Site 0137)
- Fundacion Cardiovascular de Colombia ( Site 0136)
- Fundacion Valle del Lili ( Site 0140)
- Herlev Hospital ( Site 0170)
- Aarhus Universitets hospital ( Site 0175)
- Odense Universitetshospital ( Site 0160)
- Hopital de la Croix-Rousse ( Site 0193)
- Hopital de la Timone ( Site 0188)
- CHU Bordeaux Haut-Leveque ( Site 0185)
- C.H.U. de Nancy. Hopital de Brabois Adultes ( Site 0180)
- A.P.H. Paris, Hopital Henri Mondor ( Site 0179)
- Hopital Paul Brousse ( Site 0182)
- Universitaetsklinikum Freiburg ( Site 0199)
- Krankenhaus Nord-West GmbH ( Site 0208)
- Medizinische Hochschule Hannover ( Site 0200)
- Universitaetsklinikum Bonn ( Site 0203)
- Universitaetsklinikum Halle ( Site 0213)
- Universitaetsklinikum Leipzig ( Site 0202)
- Universitaetsklinikum Schleswig-Holstein-Campus Lubeck ( Site 0215)
- Charite - Universitaetsmedizin ( Site 0204)
- Universitaetsklinikum Hamburg-Eppendorf ( Site 0207)
- Prince of Wales Hospital ( Site 0242)
- Somogy Megyei Kaposi Mór Oktató Kórház-Oncology center ( Site 0267)
- Zala Megyei Szent Rafael Korhaz ( Site 0265)
- Semmelweis University ( Site 0264)
- St Vincents University Hospital ( Site 0690)
- Emek Medical Center ( Site 0307)
- Rambam Health Care Campus-Oncology Division ( Site 0305)
- Hadassah Ein Karem Jerusalem ( Site 0303)
- Rabin Medical Center ( Site 0304)
- Sourasky Medical Center ( Site 0306)
- Ospedale del Mare ( Site 0327)
- ASST Grande Ospedale Metropolitano Niguarda-Oncologia Falck ( Site 0331)
- Ospedale Mauriziano-SCDU ONCOLOGIA MEDICA ( Site 0333)
- AOU Policlinico G. Martino ( Site 0324)
- Azienda Ospedaliera Spedali Civili di Brescia-Oncology ( Site 0334)
- Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico ( Site 0325)
- Az Osp di Rilievo Nazionale A. Cardarelli ( Site 0329)
- Azienda USL della Romagna-Dipartimento di Oncologia ed Ematologia ( Site 0332)
- Policlinico Universitario -Agostino Gemelli ( Site 0328)
- National Cancer Center Hospital East ( Site 0347)
- Ehime University Hospital ( Site 0368)
- Kurume University Hospital ( Site 0362)
- Hokkaido P.W.F.A.C Sapporo-Kosei General Hospital ( Site 0345)
- Kanazawa University Hospital ( Site 0354)
- Kagawa Prefectural Central Hospital ( Site 0364)
- Toranomon Hospital Kajigaya ( Site 0369)
- Yokohama City University Medical Center ( Site 0351)
- Kanagawa Cancer Center ( Site 0352)
- Nara Medical University Hospital ( Site 0359)
- Kindai University Hospital ( Site 0358)
- Saitama Medical University Hospital ( Site 0370)
- Shizuoka Cancer Center Hospital and Research Institute ( Site 0365)
- Jichi Medical University Hospital ( Site 0353)
- Chiba University Hospital ( Site 0346)
- National Hospital Organization Kyushu Medical Center ( Site 0361)
- Hiroshima University Hospital ( Site 0360)
- Kumamoto University ( Site 0372)
- University Hospital, Kyoto Prefectural University of Medicine ( Site 0367)
- Osaka International Cancer Institute ( Site 0357)
- Japanese Red Cross Osaka Hospital ( Site 0356)
- Saga-Ken Medical Centre Koseikan ( Site 0363)
- Toranomon Hospital ( Site 0349)
- Juntendo University Hospital ( Site 0371)
- The University of Tokyo Hospital ( Site 0348)
- Chonnam National University Hwasun Hospital ( Site 0572)
- Seoul National University Bundang Hospital ( Site 0570)
- Pusan National University Hospital ( Site 0568)
- Kyungpook National University Hospital ( Site 0569)
- Seoul National University Hospital ( Site 0567)
- Severance Hospital Yonsei University Health System ( Site 0564)
- Asan Medical Center ( Site 0565)
- Samsung Medical Center ( Site 0566)
- The Catholic University of Korea St. Mary s Hospital ( Site 0571)
- Korea University Guro Hospital ( Site 0573)
- Maastricht University Medical Centre ( Site 0440)
- AMC ( Site 0438)
- Leids Universitair Medisch Centrum-Medical Oncology ( Site 0442)
- Erasmus University Medical Center ( Site 0439)
- Universitair Medisch Centrum Utrecht-Medical Oncology ( Site 0441)
- Auckland City Hospital ( Site 0459)
- Oslo Universitetssykehus Ullevål ( Site 0500)
- Centro Hospitalar e Universitario de Coimbra ( Site 0502)
- Centro Hospitalar de Lisboa Central, EPE - Hosp St. Ant dos Capuchos ( Site 0505)
- Centro Hospitalar do Porto, E.P.E. - Hospital Geral de Sto. Antonio ( Site 0504)
- Inst. Portugues de Oncologia de Porto Francisco Gentil EPE ( Site 0503)
- Centro Hospitalar de Sao Joao. EPE - Hospital de Sao Joao ( Site 0501)
- Ad-Vance Medical Research LLC ( Site 0527)
- Puerto Rico Medical Research Center LLC ( Site 0523)
- VA Caribbean Healthcare System ( Site 0524)
- FDI Clinical Research ( Site 0522)
- Hospital Universitario Puerta de Hierro ( Site 0596)
- Hospital General Universitario de Valencia ( Site 0595)
- Hospital General Universitario Gregorio Maranon ( Site 0598)
- Hospital Ramon y Cajal ( Site 0593)
- Hospital Clinico San Carlos ( Site 0597)
- Hospital Virgen del Rocio ( Site 0591)
- Chang Gung Medical Foundation. Kaohsiung Branch ( Site 0609)
- Kaohsiung Medical University Hospital ( Site 0611)
- China Medical University Hospital-Surgical Department ( Site 0610)
- Taichung Veterans General Hospital ( Site 0613)
- National Cheng Kung University Hospital ( Site 0608)
- National Taiwan University Hospital ( Site 0606)
- Taipei Veterans General Hospital-Division of Gastroenterology & Hepatology, Department of Medicine (
- Chang Gung Medical Foundation. Linkou ( Site 0607)
- Chulalongkorn University ( Site 0627)
- Ramathibodi Hospital, Mahidol University ( Site 0628)
- Faculty of Medicine Siriraj Hospital ( Site 0629)
- Hacettepe University Medical Faculty ( Site 0653)
- Ankara City Hospital-Medical Oncology ( Site 0661)
- Trakya University Medical Faculty Balkan Oncology Hospital ( Site 0648)
- Bezmialem Vakf Üniversitesi-Oncology ( Site 0660)
- Ege University Medical Faculty Tulay Aktas Oncology Hospital ( Site 0654)
- I.E.U. Medical Point Hastanesi ( Site 0649)
- Konya Necmettin Erbakan University Medical Faculty ( Site 0652)
- Inonu Universitesi Medical Fakultesi ( Site 0650)
- Grigoriev Institute for medical Radiology NAMS of Ukraine ( Site 0673)
- Communal non profit enterprise Regional Clinical Oncology Center ( Site 0669)
- Shalimov s NI of Surgery and Transplantation ( Site 0671)
- Barts Health NHS Trust ( Site 0692)
- Royal Marsden NHS Foundation Trust ( Site 0694)
- Royal Marsden NHS Trust ( Site 0693)
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Lenvatinib plus Pembrolizumab plus TACE
Oral Placebo plus IV Placebo 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).
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).