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 Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04246177
• Other study ID #: 7902-012
• Secondary ID: MK-7902-012LEAP-
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: May 22, 2020
• Est. completion date: December 31, 2029

Study information

• Verified date: September 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 450
• Est. completion date: December 31, 2029
• Est. primary completion date: June 30, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular

Intervention

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.

Biological:
• Pembrolizumab
Administered via IV infusion at a dose of 400 mg once every 6 weeks (Q6W).

Drug:
• Oral Placebo
Lenvatinib-matching placebo administered via oral capsules once a day during each 21-day cycle.
• IV Placebo
Pembrolizumab-matching placebo administered via IV infusion once every 6 weeks (Q6W).

Procedure:
• TACE
Conducted as a background procedure of chemotherapeutic and embolic agent(s).

Locations

Country	Name	City	State
Australia	Princess Alexandra Hospital ( Site 0006)	Brisbane	Queensland
Australia	Austin Health ( Site 0008)	Heidelberg	Victoria
Australia	St George Hospital ( Site 0005)	Kogarah	New South Wales
Australia	Alfred Health ( Site 0004)	Melbourne	Victoria
Australia	Royal Perth Hospital ( Site 0002)	Perth	Western Australia
Australia	Westmead Hospital-Gastroenterology & Hepatology ( Site 0009)	Westmead	New South Wales
Brazil	Fundação Pio XII - Hospital de Câncer de Barretos-Unidade de Pesquisa Clínica ( Site 0058)	Barretos	Sao Paulo
Brazil	Clinica de Oncologia Reichow ( Site 0052)	Blumenau	Santa Catarina
Brazil	Fundacao Dr Amaral Carvalho ( Site 0050)	JAU	Sao Paulo
Brazil	Liga Norte Riograndense Contra o Câncer-Centro de Pesquisa Clínica ( Site 0057)	Natal	Rio Grande Do Norte
Brazil	Hospital Nossa Senhora da Conceição-Centro Integrado de Pesquisa em Oncologia ( Site 0056)	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital de Base de Sao Jose de Rio Preto ( Site 0043)	Sao Jose do Rio Preto	Sao Paulo
Brazil	A.C. Camargo Cancer Center ( Site 0054)	Sao Paulo
Brazil	BP - A Beneficencia Portuguesa de São Paulo ( Site 0046)	São Paulo	Sao Paulo
Chile	Bradfordhill ( Site 0066)	Santiago	Region M. De Santiago
Chile	Centro de Cancer Nuestra Senora de la Esperanza ( Site 0065)	Santiago	Region M. De Santiago
Chile	Centro de Oncología de Precisión-Oncology ( Site 0068)	Santiago	Region M. De Santiago
Chile	Centro Investigación del Cáncer James Lind ( Site 0064)	Temuco	Araucania
China	Beijing Cancer Hospital ( Site 0099)	Beijing	Beijing
China	Beijing Cancer Hospital ( Site 0105)	Beijing	Beijing
China	Peking Union Medical College Hospital ( Site 0087)	Beijing	Beijing
China	Hunan Cancer Hospital ( Site 0096)	Changsha	Hunan
China	Hunan Provincial People's Hospital ( Site 0113)	Changsha	Hunan
China	West China Hospital of Sichuan University ( Site 0119)	Chengdu	Sichuan
China	Chinese People s Liberation Army Army Characteristic Medical Center ( Site 0117)	Chongqing	Chongqing
China	Fujian Provincial Cancer Hospital ( Site 0085)	Fuzhou	Fujian
China	Mengchao Hepatobiliary Hospital of Fujian Medical University ( Site 0121)	Fuzhou	Fujian
China	The First Affiliated Hospital of Fujian Medical University ( Site 0089)	Fuzhou	Fujian
China	Guangdong Provincial People s Hospital ( Site 0100)	Guangzhou	Guangdong
China	Nanfang Hospital of Southern Medical University ( Site 0088)	Guangzhou	Guangdong
China	SUN YAT-SEN UNIVERSITY CANCER CENTRE-Department of Medical Imaging and Interventional Radiology ( Si	Guangzhou	Guangdong
China	Zhujiang Hospital of Southern Medical University ( Site 0115)	Guangzhou	Guangdong
China	Hainan General Hospital ( Site 0112)	Haikou	Hainan
China	2nd Affil Hosp of Zhejiang University College of Medicine ( Site 0110)	Hangzhou	Zhejiang
China	Sir Run Run Shaw Hospital ( Site 0094)	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital ( Site 0103)	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital ( Site 0090)	Harbin	Heilongjiang
China	Anhui Provincial Hospital ( Site 0092)	Heifei	Anhui
China	The First Hospital of Kunming ( Site 0124)	Kunming	Yunnan
China	Jiangxi Provincial Cancer Hospital-Cancer Hospital ( Site 0134)	Nanchang	Jiangxi
China	Guangxi Medical University Affiliated Tumor Hospital-Hepatological surgery ( Site 0862)	Nanning	Guangxi
China	Ningbo Medical Center ( Site 0132)	Ningbo	Zhejiang
China	Fudan University Shanghai Cancer Center ( Site 0106)	Shanghai	Shanghai
China	The Third Affiliated Hospital of Naval Medical University ( Site 0123)	Shanghai	Shanghai
China	Zhongshan Hospital Fudan University ( Site 0084)	Shanghai	Shanghai
China	Suining Central Hospital ( Site 0857)	Suining	Sichuan
China	The First Affiliated Hospital of Soochow University ( Site 0120)	Suzhou	Jiangsu
China	Tianjin Medical University Cancer Institute & Hospital ( Site 0098)	Tianjin	Tianjin
China	Tianjin Third Central Hospital ( Site 0861)	Tianjin	Tianjin
China	Chongqing Three Gorges Central Hospital ( Site 0859)	Wanzhou	Chongqing
China	Hubei Cancer Hospital ( Site 0101)	Wuhan	Hubei
China	Tongji Hospital Tongji Medical,Science & Technology ( Site 0126)	Wuhan	Hubei
China	The First Affiliated Hospital of Xi an Jiaotong University ( Site 0108)	XI An	Shanxi
China	Xi'an International Medical Center Hospital ( Site 0860)	Xi'an	Shaanxi
China	Zhongshan Hospital Fudan University (Xiamen Branch) ( Site 0133)	Xiamen	Fujian
China	Henan Cancer Hospital ( Site 0114)	Zhengzhou	Henan
China	Jinan University - Zhuhai People's Hospital-Intervention Department ( Site 0856)	Zhuhai	Guangdong
Colombia	Administradora Country S.A. ( Site 0137)	Bogota	Distrito Capital De Bogota
Colombia	Fundacion Valle del Lili ( Site 0140)	Cali	Valle Del Cauca
Colombia	Hospital Pablo Tobon Uribe ( Site 0145)	Medellin	Antioquia
Colombia	Fundacion Cardiovascular de Colombia ( Site 0136)	Piedecuesta	Santander
Denmark	Aarhus Universitets hospital ( Site 0175)	Aarhus N	Midtjylland
Denmark	Herlev Hospital ( Site 0170)	Herlev	Hovedstaden
Denmark	Odense Universitetshospital ( Site 0160)	Odense	Syddanmark
France	A.P.H. Paris, Hopital Henri Mondor ( Site 0179)	Creteil	Val-de-Marne
France	Hopital de la Croix-Rousse ( Site 0193)	Lyon	Auvergne
France	Hopital de la Timone ( Site 0188)	Marseille	Bouches-du-Rhone
France	CHU Bordeaux Haut-Leveque ( Site 0185)	Pessac Cedex	Gironde
France	C.H.U. de Nancy. Hopital de Brabois Adultes ( Site 0180)	Vandoeuvre les Nancy	Meurthe-et-Moselle
France	Hopital Paul Brousse ( Site 0182)	Villejuif	Val-de-Marne
Germany	Charite - Universitaetsmedizin ( Site 0204)	Berlin
Germany	Universitaetsklinikum Bonn ( Site 0203)	Bonn	Nordrhein-Westfalen
Germany	Krankenhaus Nord-West GmbH ( Site 0208)	Frankfurt am Main	Hessen
Germany	Universitaetsklinikum Freiburg ( Site 0199)	Freiburg	Baden-Wurttemberg
Germany	Universitaetsklinikum Halle ( Site 0213)	Halle (Saale)	Sachsen-Anhalt
Germany	Universitaetsklinikum Hamburg-Eppendorf ( Site 0207)	Hamburg
Germany	Medizinische Hochschule Hannover ( Site 0200)	Hannover	Niedersachsen
Germany	Universitaetsklinikum Leipzig ( Site 0202)	Leipzig	Sachsen
Germany	Universitaetsklinikum Schleswig-Holstein-Campus Lubeck ( Site 0215)	Luebeck	Schleswig-Holstein
Hong Kong	Prince of Wales Hospital ( Site 0242)	Shatin
Hungary	Semmelweis University ( Site 0264)	Budapest
Hungary	Somogy Megyei Kaposi Mór Oktató Kórház-Oncology center ( Site 0267)	Kaposvár	Somogy
Hungary	Zala Megyei Szent Rafael Korhaz ( Site 0265)	Zalaegerszeg	Zala
Ireland	St Vincents University Hospital ( Site 0690)	Dublin
Israel	Emek Medical Center ( Site 0307)	Afula
Israel	Rambam Health Care Campus-Oncology Division ( Site 0305)	Haifa
Israel	Hadassah Ein Karem Jerusalem ( Site 0303)	Jerusaelm
Israel	Rabin Medical Center ( Site 0304)	Petah Tikva
Israel	Sourasky Medical Center ( Site 0306)	Tel Aviv
Italy	Azienda Ospedaliera Spedali Civili di Brescia-Oncology ( Site 0334)	Brescia
Italy	AOU Policlinico G. Martino ( Site 0324)	Messina	Sicilia
Italy	ASST Grande Ospedale Metropolitano Niguarda-Oncologia Falck ( Site 0331)	Milan	Milano
Italy	Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico ( Site 0325)	Milano
Italy	Az Osp di Rilievo Nazionale A. Cardarelli ( Site 0329)	Napoli
Italy	Ospedale del Mare ( Site 0327)	Napoli	Campania
Italy	Azienda USL della Romagna-Dipartimento di Oncologia ed Ematologia ( Site 0332)	Ravenna
Italy	Policlinico Universitario -Agostino Gemelli ( Site 0328)	Roma
Italy	Ospedale Mauriziano-SCDU ONCOLOGIA MEDICA ( Site 0333)	Torino	Piemonte
Japan	Chiba University Hospital ( Site 0346)	Chiba
Japan	National Hospital Organization Kyushu Medical Center ( Site 0361)	Fukuoka
Japan	Hiroshima University Hospital ( Site 0360)	Hiroshima
Japan	Saitama Medical University Hospital ( Site 0370)	Iruma-gun	Saitama
Japan	Kanazawa University Hospital ( Site 0354)	Kanazawa	Ishikawa
Japan	Nara Medical University Hospital ( Site 0359)	Kashihara	Nara
Japan	National Cancer Center Hospital East ( Site 0347)	Kashiwa	Chiba
Japan	Toranomon Hospital Kajigaya ( Site 0369)	Kawasaki	Kanagawa
Japan	Kumamoto University ( Site 0372)	Kumamoto
Japan	Kurume University Hospital ( Site 0362)	Kurume	Fukuoka
Japan	University Hospital, Kyoto Prefectural University of Medicine ( Site 0367)	Kyoto
Japan	Japanese Red Cross Osaka Hospital ( Site 0356)	Osaka
Japan	Osaka International Cancer Institute ( Site 0357)	Osaka
Japan	Kindai University Hospital ( Site 0358)	Osakasayama	Osaka
Japan	Saga-Ken Medical Centre Koseikan ( Site 0363)	Saga
Japan	Hokkaido P.W.F.A.C Sapporo-Kosei General Hospital ( Site 0345)	Sapporo	Hokkaido
Japan	Jichi Medical University Hospital ( Site 0353)	Shimotsuke	Tochigi
Japan	Shizuoka Cancer Center Hospital and Research Institute ( Site 0365)	Sunto-gun	Shizuoka
Japan	Kagawa Prefectural Central Hospital ( Site 0364)	Takamatsu	Kagawa
Japan	Juntendo University Hospital ( Site 0371)	Tokyo
Japan	The University of Tokyo Hospital ( Site 0348)	Tokyo
Japan	Toranomon Hospital ( Site 0349)	Tokyo
Japan	Ehime University Hospital ( Site 0368)	Toon	Ehime
Japan	Kanagawa Cancer Center ( Site 0352)	Yokohama	Kanagawa
Japan	Yokohama City University Medical Center ( Site 0351)	Yokohama	Kanagawa
Korea, Republic of	Pusan National University Hospital ( Site 0568)	Busan	Pusan-Kwangyokshi
Korea, Republic of	Kyungpook National University Hospital ( Site 0569)	Daegu	Taegu-Kwangyokshi
Korea, Republic of	Chonnam National University Hwasun Hospital ( Site 0572)	Hwasun	Jeonranamdo
Korea, Republic of	Seoul National University Bundang Hospital ( Site 0570)	Seongnam-si	Kyonggi-do
Korea, Republic of	Asan Medical Center ( Site 0565)	Seoul
Korea, Republic of	Korea University Guro Hospital ( Site 0573)	Seoul
Korea, Republic of	Samsung Medical Center ( Site 0566)	Seoul
Korea, Republic of	Seoul National University Hospital ( Site 0567)	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System ( Site 0564)	Seoul
Korea, Republic of	The Catholic University of Korea St. Mary s Hospital ( Site 0571)	Seoul
Netherlands	AMC ( Site 0438)	Amsterdam	Noord-Holland
Netherlands	Leids Universitair Medisch Centrum-Medical Oncology ( Site 0442)	Leiden	Zuid-Holland
Netherlands	Maastricht University Medical Centre ( Site 0440)	Maastricht	Limburg
Netherlands	Erasmus University Medical Center ( Site 0439)	Rotterdam	Zuid-Holland
Netherlands	Universitair Medisch Centrum Utrecht-Medical Oncology ( Site 0441)	Utrecht
New Zealand	Auckland City Hospital ( Site 0459)	Auckland
Norway	Oslo Universitetssykehus Ullevål ( Site 0500)	Oslo
Portugal	Centro Hospitalar e Universitario de Coimbra ( Site 0502)	Coimbra
Portugal	Centro Hospitalar de Lisboa Central, EPE - Hosp St. Ant dos Capuchos ( Site 0505)	Lisboa
Portugal	Centro Hospitalar de Sao Joao. EPE - Hospital de Sao Joao ( Site 0501)	Porto
Portugal	Centro Hospitalar do Porto, E.P.E. - Hospital Geral de Sto. Antonio ( Site 0504)	Porto
Portugal	Inst. Portugues de Oncologia de Porto Francisco Gentil EPE ( Site 0503)	Porto
Puerto Rico	Ad-Vance Medical Research LLC ( Site 0527)	Ponce
Puerto Rico	FDI Clinical Research ( Site 0522)	San Juan
Puerto Rico	Puerto Rico Medical Research Center LLC ( Site 0523)	San Juan
Puerto Rico	VA Caribbean Healthcare System ( Site 0524)	San Juan
Spain	Hospital Clinico San Carlos ( Site 0597)	Madrid
Spain	Hospital General Universitario Gregorio Maranon ( Site 0598)	Madrid
Spain	Hospital Ramon y Cajal ( Site 0593)	Madrid
Spain	Hospital Universitario Puerta de Hierro ( Site 0596)	Majadahonda	Madrid
Spain	Hospital Virgen del Rocio ( Site 0591)	Sevilla
Spain	Hospital General Universitario de Valencia ( Site 0595)	Valencia	Valenciana, Comunitat
Taiwan	Kaohsiung Medical University Hospital ( Site 0611)	Kaohsiung
Taiwan	Chang Gung Medical Foundation. Kaohsiung Branch ( Site 0609)	Kaohsiung City	Kaohsiung
Taiwan	China Medical University Hospital-Surgical Department ( Site 0610)	Taichung
Taiwan	Taichung Veterans General Hospital ( Site 0613)	Taichung
Taiwan	National Cheng Kung University Hospital ( Site 0608)	Tainan
Taiwan	National Taiwan University Hospital ( Site 0606)	Taipei
Taiwan	Taipei Veterans General Hospital-Division of Gastroenterology & Hepatology, Department of Medicine (	Taipei
Taiwan	Chang Gung Medical Foundation. Linkou ( Site 0607)	Taoyuan
Thailand	Chulalongkorn University ( Site 0627)	Bangkok	Krung Thep Maha Nakhon
Thailand	Faculty of Medicine Siriraj Hospital ( Site 0629)	Bangkok	Krung Thep Maha Nakhon
Thailand	Ramathibodi Hospital, Mahidol University ( Site 0628)	Bangkok	Krung Thep Maha Nakhon
Turkey	Ankara City Hospital-Medical Oncology ( Site 0661)	Ankara
Turkey	Hacettepe University Medical Faculty ( Site 0653)	Ankara
Turkey	Trakya University Medical Faculty Balkan Oncology Hospital ( Site 0648)	Edirne
Turkey	Bezmialem Vakf Üniversitesi-Oncology ( Site 0660)	Istanbul
Turkey	Ege University Medical Faculty Tulay Aktas Oncology Hospital ( Site 0654)	Izmir
Turkey	I.E.U. Medical Point Hastanesi ( Site 0649)	Izmir
Turkey	Konya Necmettin Erbakan University Medical Faculty ( Site 0652)	Konya
Turkey	Inonu Universitesi Medical Fakultesi ( Site 0650)	Malatya
Ukraine	Communal non profit enterprise Regional Clinical Oncology Center ( Site 0669)	Kharkiv	Kharkivska Oblast
Ukraine	Grigoriev Institute for medical Radiology NAMS of Ukraine ( Site 0673)	Kharkiv	Kharkivska Oblast
Ukraine	Shalimov s NI of Surgery and Transplantation ( Site 0671)	Kyiv	Kyivska Oblast
United Kingdom	Barts Health NHS Trust ( Site 0692)	London	London, City Of
United Kingdom	Royal Marsden NHS Foundation Trust ( Site 0694)	London	London, City Of
United Kingdom	Royal Marsden NHS Trust ( Site 0693)	Sutton	London, City Of
United States	University of New Mexico Comprehensive Cancer Center ( Site 0805)	Albuquerque	New Mexico
United States	Mountain States Tumor Institute ( Site 0773)	Boise	Idaho
United States	University of Cincinnati Medical Center ( Site 0791)	Cincinnati	Ohio
United States	The Ohio State University Wexner Medical Center ( Site 0759)	Columbus	Ohio
United States	Henry Ford Hospital-GI/Hepatology Research ( Site 0735)	Detroit	Michigan
United States	Penn State Hershey Medical Center ( Site 0766)	Hershey	Pennsylvania
United States	Houston Methodist Research Institute ( Site 0784)	Houston	Texas
United States	Edwards Comprehensive Cancer Center ( Site 0786)	Huntington	West Virginia
United States	University of Iowa Hospital and Clinics ( Site 0729)	Iowa City	Iowa
United States	Scripps Clinic Torrey Pines ( Site 0714)	La Jolla	California
United States	Monter Cancer Center ( Site 0780)	Lake Success	New York
United States	UCLA Hematology/Oncology - Santa Monica ( Site 0720)	Los Angeles	California
United States	USC Norris Comprehensive Cancer Center ( Site 0717)	Los Angeles	California
United States	University of Louisville ( Site 0757)	Louisville	Kentucky
United States	Yale Cancer Center ( Site 0724)	New Haven	Connecticut
United States	Tulane Medical Center ( Site 0787)	New Orleans	Louisiana
United States	University Medical Center New Orleans ( Site 0733)	New Orleans	Louisiana
United States	Icahn School of Medicine at Mount Sinai ( Site 0744)	New York	New York
United States	Stephenson Cancer Center ( Site 0745)	Oklahoma City	Oklahoma
United States	UC Irvine Health ( Site 0718)	Orange	California
United States	OHSU Center for Health & Healing ( Site 0746)	Portland	Oregon
United States	Saint Louis University ( Site 0769)	Saint Louis	Missouri
United States	ProMedica Flower Hospital ( Site 0796)	Sylvania	Ohio
United States	Tampa General Hospital ( Site 0764)	Tampa	Florida
United States	Arizona Oncology Associates PC- HOPE ( Site 0770)	Tucson	Arizona
United States	University of Kansas Cancer Center ( Site 0731)	Westwood	Kansas
United States	Wake Forest Baptist Health ( Site 0741)	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC	Eisai Inc.

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Chile,  China,  Colombia,  Denmark,  France,  Germany,  Hong Kong,  Hungary,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  New Zealand,  Norway,  Portugal,  Puerto Rico,  Spain,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to ~95 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Merck Oncology Clinical Trials Information
•   Plain Language Summary