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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)

Primary Purpose

Carcinoma, Hepatocellular

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
lenvatinib
pembrolizumab
saline placebo
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

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), programmed cell death ligand 2 (PD-L2, PDL2)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The University of Arizona Cancer Center - North Campus ( Site 0621)
  • City of Hope Comprehensive Cancer Center ( Site 0587)
  • Scripps Health ( Site 0644)
  • Pacific Hematology Oncology Associates ( Site 0588)
  • UCLA ( Site 0589)
  • Georgetown University ( Site 0594)
  • University of Miami, Sylvester Comprehensive Cancer Center ( Site 0596)
  • Advent Health ( Site 0595)
  • Tampa General Medical Group ( Site 0629)
  • Emory University Winship Cancer Institute ( Site 0639)
  • University of Kansas Cancer Center ( Site 0600)
  • Massachusetts General Hospital ( Site 0603)
  • Beth Israel Deaconess Medical Center ( Site 0716)
  • Icahn School of Medicine at Mount Sinai ( Site 0611)
  • University of Rochester ( Site 0613)
  • Stony Brook University Medical Center - Cancer Center ( Site 0612)
  • University of Oklahoma Health Science Center ( Site 0625)
  • Oregon Health & Science University ( Site 0645)
  • Eastern Regional Medical Center, Inc. ( Site 0626)
  • Central Texas Veterans Healthcare System ( Site 0617)
  • Cancer Care Northwest ( Site 0636)
  • Royal Prince Alfred Hospital ( Site 0001)
  • Princess Alexandra Hospital ( Site 0007)
  • Monash Health-Monash Medical Centre ( Site 0004)
  • St Vincents Hospital Melbourne ( Site 0003)
  • Liverpool Hospital. ( Site 0002)
  • BC Cancer-Vancouver Center ( Site 0056)
  • London Health Sciences Centre ( Site 0053)
  • Sunnybrook Research Institute ( Site 0055)
  • Princess Margaret Cancer Centre ( Site 0050)
  • McGill University Health Centre ( Site 0052)
  • Clinica Universidad Catolica del Maule ( Site 0065)
  • Fundacion Arturo Lopez Perez ( Site 0064)
  • Pontificia Universidad Catolica de Chile ( Site 0070)
  • Instituto Clinico Oncologico del Sur ( Site 0067)
  • First Affiliated Hospital of Anhui Medical University ( Site 0095)
  • Cancer Hospital Chinese Academy of Medical Sciences ( Site 0100)
  • Beijing Cancer Hospital ( Site 0088)
  • 900 Hospital of the Joint ( Site 0091)
  • Guangdong General Hospital ( Site 0092)
  • Southern Medical University Nanfang Hospital ( Site 0102)
  • Harbin Medical University Cancer Hospital ( Site 0089)
  • Wuhan Union hospital Cancer Center ( Site 0105)
  • Hunan Cancer Hospital ( Site 0094)
  • The Third Xiangya Hospital of Central South University ( Site 0093)
  • The 81st Hospital of PLA ( Site 0085)
  • Fudan University Shanghai Cancer Center ( Site 0086)
  • The First Affiliated Hospital of Xi an Jiaotong University ( Site 0090)
  • West China Hospital of Sichuan University ( Site 0087)
  • Affiliated Tumor Hospital of Xinjiang Medical University ( Site 0109)
  • The First Affiliated Hospital of Zhejiang University ( Site 0097)
  • Sir Run Run Shaw Hospital ( Site 0110)
  • Zhejiang Cancer Hospital ( Site 0101)
  • Zhongshan Hospital Fudan University ( Site 0096)
  • Fundacion Centro de Investigacion Clinica CIC ( Site 0141)
  • Hospital Pablo Tobon Uribe ( Site 0144)
  • Hospital General de Medellin Luz Castro de Gutierrez ( Site 0137)
  • Biomelab S A S ( Site 0145)
  • Administradora Country SA - Clinica del Country ( Site 0146)
  • Instituto Nacional de Cancerologia E.S.E ( Site 0142)
  • Fundacion Valle del Lili ( Site 0140)
  • Centro Medico Imbanaco de Cali S.A ( Site 0139)
  • Institut Sainte Catherine ( Site 0167)
  • Hopital Beaujon ( Site 0160)
  • CHU Henri Mondor ( Site 0162)
  • CHRU de Lille - Hopital Claude Huriez ( Site 0159)
  • Hopital de la Croix Rousse ( Site 0157)
  • Hopital Saint Joseph ( Site 0166)
  • Centre Hospitalier Regional du Orleans ( Site 0169)
  • Centre Eugene Marquis ( Site 0158)
  • CHU de Nancy Hopital Brabois Adultes ( Site 0164)
  • Klinikum der Universitaet Aachen - RWTH ( Site 0185)
  • Universitaetsklinikum Carl Gustav Carus der TU Dresden ( Site 0178)
  • Universitaetsklinikum Essen ( Site 0188)
  • Universitaetsklinikum Frankfurt ( Site 0180)
  • Universitaetsklinikum Hamburg-Eppendorf ( Site 0184)
  • Universitaetsklinik Koeln ( Site 0189)
  • Universitaetsklinikum Leipzig ( Site 0187)
  • Otto-Von-Guericke-Universitaet Magdeburg ( Site 0182)
  • Universitaetsklinikum Tuebingen ( Site 0179)
  • Universitaetsklinikum Wuerzburg ( Site 0186)
  • St Vincents University Hospital ( Site 0242)
  • Mater Misericordiae University Hospital ( Site 0241)
  • Ospedale Sacro Cuore - Don Calabria ( Site 0289)
  • Centro di Riferimento Oncologico de Aviano Istituto Nazionale Tumori ( Site 0292)
  • Policlinico S. Orsola-Malpighi ( Site 0286)
  • Istituto Oncologico Veneto ( Site 0287)
  • Az Osp Univ Policlin Paolo Giaccone ( Site 0284)
  • Fondazione Salvatore Maugeri IRCCS. ( Site 0290)
  • Azienda Ospedaliero-Univers. Pisana Ospedale S. Chiara ( Site 0291)
  • Policlinico Universitario Campus Biomedico ( Site 0288)
  • Aichi Cancer Center Hospital ( Site 0316)
  • National Cancer Center Hospital East ( Site 0306)
  • Kurume University Hospital ( Site 0322)
  • Hokkaido P.W.F.A.C Sapporo-Kosei General Hospital ( Site 0304)
  • Kanazawa University Hospital ( Site 0315)
  • Kagawa University Hospital ( Site 0324)
  • Kagawa Prefectural Central Hospital ( Site 0325)
  • Toranomon Hospital Kajigaya ( Site 0312)
  • Yokohama City University Medical Center ( Site 0313)
  • Kanagawa Cancer Center ( Site 0314)
  • Kindai University Hospital ( Site 0319)
  • Kyorin University Hospital ( Site 0309)
  • Musashino Red Cross Hospital ( Site 0310)
  • Chiba University Hospital ( Site 0305)
  • National Hospital Organization Kyushu Medical Center ( Site 0321)
  • Hiroshima University Hospital ( Site 0320)
  • Osaka Red Cross Hospital ( Site 0317)
  • Saga-Ken Medical Centre Koseikan ( Site 0323)
  • National Cancer Center Hospital ( Site 0307)
  • Toranomon Hospital ( Site 0311)
  • The University of Tokyo Hospital ( Site 0308)
  • Wakayama Medical University Hospital ( Site 0318)
  • Seoul National University Bundang Hospital ( Site 0464)
  • Seoul National University Hospital ( Site 0462)
  • Yonsei University Severance Hospital ( Site 0463)
  • Asan Medical Center ( Site 0460)
  • Samsung Medical Center ( Site 0461)
  • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 0363)
  • Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 0365)
  • Centro de Investigacion Medica Aguascalientes ( Site 0355)
  • Medical Care and Research S.A. de C.V. ( Site 0359)
  • CRYPTEX Investigacion Clinica S.A. de C.V. ( Site 0362)
  • Oaxaca Site Management Organization S.C. ( Site 0366)
  • Unidad Medica Oncologica ( Site 0369)
  • Auckland City Hospital ( Site 0376)
  • Christchurch Hospital ( Site 0377)
  • Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu ( Site 0419)
  • Szpital Wojewodzki w Koszalinie im. Mikolaja Kopernika ( Site 0421)
  • ID Clinic ( Site 0431)
  • Ars Medical Sp. z o.o. ( Site 0433)
  • MTZ Clinical Research Sp. z o. o. ( Site 0427)
  • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0418)
  • N.N. Blokhin NMRCO ( Site 0439)
  • First Moscow State Medical University n.a. I.M.Sechenov ( Site 0453)
  • Railway Hospital of OJSC ( Site 0447)
  • City Clinical Oncology Center ( Site 0446)
  • Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0450)
  • Pyatigorsk Oncology Dispensary ( Site 0441)
  • Hospital Universitari Vall d Hebron ( Site 0508)
  • Hospital Universitario Puerta de Hierro ( Site 0513)
  • Hospital General Universitario Gregorio Maranon ( Site 0504)
  • Hospital Universitario Ramon y Cajal ( Site 0514)
  • Hospital Universitario La Paz ( Site 0510)
  • Complejo Hospitalario Universitario de Santiago ( Site 0506)
  • Hospital Universitario Virgen del Rocio ( Site 0509)
  • Hospital Universitario y Politecnico La Fe de Valencia ( Site 0505)
  • Kaohsiung Medical University Chung-Ho Memorial Hospital ( Site 0529)
  • China Medical University Hospital ( Site 0527)
  • Taichung Veterans General Hospital ( Site 0526)
  • National Cheng Kung University Hospital ( Site 0528)
  • National Taiwan University Hospital ( Site 0523)
  • Taipei Veterans General Hospital ( Site 0524)
  • Chang Gung Medical Foundation. Linkou ( Site 0525)
  • Siriraj Hospital. Mahidol Univerisity ( Site 0213)
  • Songklanagarind Hospital ( Site 0214)
  • Chiang Mai University Maharaj Nakorn Chiang Mai Hospital ( Site 0211)
  • Adana Sehir Hastanesi ( Site 0549)
  • Hacettepe Uni. Tip Fakultesi ( Site 0553)
  • Abdurrahman Yurtaslan Onkoloji Hastanesi ( Site 0551)
  • Akdeniz Universitesi Tip Fakultesi ( Site 0548)
  • Trakya Universitesi Tip Fakultesi ( Site 0544)
  • Erzurum Ataturk University Faculty of Medicine ( Site 0546)
  • Bezmi Alem Universitesi Tıp Fakultesi ( Site 0547)
  • Necmettin Erbakan Universitesi Meram Tip Fakultesi ( Site 0550)
  • Inonu Universitesi Medical Fakultesi ( Site 0545)
  • Royal Free London NHS Foundation Trust ( Site 0567)
  • Kings College Hospital NHS Foundation Trust ( Site 0565)
  • The Clatterbridge Cancer Centre NHS Foundation Trust ( Site 0573)
  • The Beatson West of Scotland Cancer Centre ( Site 0566)
  • The Christie NHS Foundation Trust ( Site 0575)
  • Nottingham University Hospitals NHS Trust ( Site 0569)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

lenvatinib plus pembrolizumab

lenvatinib plus placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.
Overall Survival (OS)
OS was defined as the time from randomization until death from any cause

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
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.
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
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
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
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.
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
Number of participants who discontinued study treatment due to an AE

Full Information

First Posted
October 18, 2018
Last Updated
July 21, 2023
Sponsor
Merck Sharp & Dohme LLC
Collaborators
Eisai Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03713593
Brief Title
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)
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 31, 2018 (Actual)
Primary Completion Date
June 21, 2022 (Actual)
Study Completion Date
August 29, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
Collaborators
Eisai Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Hepatocellular
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)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
794 (Actual)

8. Arms, Groups, and Interventions

Arm Title
lenvatinib plus pembrolizumab
Arm Type
Experimental
Arm Description
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.
Arm Title
lenvatinib plus placebo
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
lenvatinib
Other Intervention Name(s)
MK-7902, E7080, LENVIMA®
Intervention Description
Administered orally once a day
Intervention Type
Biological
Intervention Name(s)
pembrolizumab
Other Intervention Name(s)
MK-3475, KEYTRUDA®
Intervention Description
Administered as an IV infusion on Day 1 Q3W
Intervention Type
Drug
Intervention Name(s)
saline placebo
Intervention Description
Administered as an IV infusion on Day 1 Q3W
Primary Outcome Measure Information:
Title
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Description
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.
Time Frame
Up to approximately 41 months
Title
Overall Survival (OS)
Description
OS was defined as the time from randomization until death from any cause
Time Frame
Up to approximately 41 months
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Description
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.
Time Frame
Up to approximately 41 months
Title
Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Description
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.
Time Frame
Up to approximately 41 months
Title
Disease Control Rate (DCR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Description
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.
Time Frame
Up to approximately 41 months
Title
Time to Disease Progression (TTP) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Description
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.
Time Frame
Up to approximately 41 months
Title
Progression-free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
Description
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.
Time Frame
Up to approximately 41 months
Title
Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
Description
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.
Time Frame
Up to approximately 41 months
Title
Duration of Response (DOR) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
Description
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.
Time Frame
Up to approximately 41 months
Title
Disease Control Rate (DCR) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
Description
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.
Time Frame
Up to approximately 41 months
Title
Time to Disease Progression (TTP) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
Description
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.
Time Frame
Up to approximately 41 months
Title
Number of Participants Who Experienced an Adverse Event (AE)
Description
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
Time Frame
Up to approximately 41 months
Title
Number of Participants Who Experienced an Serious Adverse Event (SAE)
Description
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
Time Frame
Up to approximately 41 months
Title
Number of Participants Who Experienced an Immune-related Adverse Event (irAE) of Clinical Interest
Description
Number of participants who experienced an AE representing an immunologic etiology and considered to be causally related to drug exposure
Time Frame
Up to approximately 41 months
Title
Number of Participants Who Experienced an Hepatic Event of Clinical Interest (HECI)
Description
Number of participants who experienced a hepatic ECI not due to disease progression as judged by the investigator.
Time Frame
Up to approximately 41 months
Title
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
Description
Number of participants who discontinued study treatment due to an AE
Time Frame
Up to approximately 41 months

10. Eligibility

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

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Links:
URL
http://merckoncologyclinicaltrials.com
Description
Merck Oncology Clinical Trial Information

Learn more about this trial

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)

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