Clinical trial NCT03867084: Safety and Efficacy of Pembrolizumab (MK-3475) Versus Placebo as Adjuvant Therapy in Participants With Hepatocellular Carcinoma (HCC) and Complete Radiological Response After Surgical Resection or Local Ablation (MK-3475-937 / KEYNOTE-937)
Official title: A Phase 3 Double-blinded, Two-arm Study to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) Versus Placebo as Adjuvant Therapy in Participants With Hepatocellular Carcinoma and Complete Radiological Response After Surgical Resection or Local Ablation (KEYNOTE-937)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hepatocellular Carcinoma
Keywords: Programmed Cell Death 1 (PD-1, PD1)
Programmed Cell Death Ligand 1 (PD-L1, PDL1)
Checkpoint Inhibitor
Immunotherapy
Adjuvant
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2019-03-07
Enrollment: 950
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety and efficacy of pembrolizumab (MK-3475) versus placebo as adjuvant therapy in participants with hepatocellular carcinoma (HCC) and complete radiological response after surgical resection or local ablation. The primary hypotheses of this study are that adjuvant pembrolizumab is superior to placebo with respect to: 1) recurrence-free survival (RFS) as assessed by blinded independent central review (BICR); and 2) overall survival (OS).


Eligibility criteria: Inclusion Criteria:

* Has a diagnosis of HCC by radiological criteria and/or pathological confirmation.
* Has an eligibility scan (CT of the chest, triphasic CT scan or MRI of the abdomen, and CT or MRI of the pelvis) confirming complete radiological response ≥4 weeks after complete surgical resection or local ablation. Randomization needs to occur within 12 weeks of the date of surgical resection or local ablation.
* Has no radiologic evidence of disease prior to enrollment.
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to Cycle 1, Day 1.
* Has a Child-Pugh class A liver score (5 to 6 points) within 7 days prior to Cycle 1, Day 1.
* Has alpha fetoprotein (AFP) concentration lower than 400 ng/mL within 28 days prior to Cycle 1, Day 1.
* Has controlled hepatitis B (Hep B).
* Has recovered adequately from toxicity and/or complications from the local intervention (surgical resection or local ablation) prior to starting study treatment.
* If female, is not pregnant or breastfeeding, and at least one of the following conditions applies: 1) Is not a woman of childbearing potential (WOCBP); or 2) Is a WOCBP and using a contraceptive method that is highly effective or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (a WOCBP must have a negative pregnancy test within 72 hours before the first dose of study treatment).
* If undergoing surgical resection, has submitted a tumor tissue sample during Screening.
* Has adequate organ function.

Exclusion Criteria:

* Has a known additional malignancy that is progressing or has required active antineoplastic treatment (including hormonal) or surgery within the past 3 years.
* Has had esophageal or gastric variceal bleeding within the last 6 months.
* Has clinically apparent ascites on physical examination.
* Has had clinically diagnosed hepatic encephalopathy in the last 6 months.
* Has received local therapy to liver ablation other than with radiofrequency or microwave ablation.
* Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
* Has an active infection requiring systemic therapy.
* Has dual active Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection at study entry.
* Has a known history of human immunodeficiency virus (HIV) infection.
* Has known active tuberculosis (TB; Bacillus tuberculosis).
* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
* Has received prior systemic anti-cancer therapy for HCC including investigational agents.
* Is receiving any of the following prohibited concomitant therapies:1) Antineoplastic systemic chemotherapy or biological therapy; 2) Immunotherapy not specified in this protocol; 3) Investigational agents other than pembrolizumab; 4) Radiation therapy; 5) Oncological surgical therapy; or systemic glucocorticoids for any purpose other than to modulate symptoms from an AE that is suspected to have an immunologic etiology.
* Has received a live vaccine within 30 days prior to the first dose of study treatment.
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to Cycle 1, Day 1.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to Cycle 1, Day 1.
* Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
* Has an active autoimmune disease that has required systemic treatment in past 2 years.
* Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
* Has had an allogenic tissue/solid organ transplant.

Primary outcomes:
measure: Recurrence-Free Survival (RFS)
timeFrame: Up to ~6 years
measure: Overall Survival (OS)
timeFrame: Up to ~8 years
Secondary outcomes:
measure: Percentage of Participants who Experience an Adverse Event (AE)
timeFrame: Up to ~8 years
measure: Percentage of Participants who Discontinue Study Treatment Due to an AE
timeFrame: Up to ~1 year
measure: Change from Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Combined Global Health Status (GHS) / Quality of Life (QoL) Scale Score
timeFrame: Baseline and time of last patient reported outcome (PRO) assessment (up to ~5 years)
measure: Change from Baseline in EORTC QLQ-Hepatocellular Carcinoma Module (EORTC QLQ-HCC18) Scale Score
timeFrame: Baseline and time of last PRO assessment (up to ~5 years)
measure: Change from Baseline in European Quality of Life (EuroQoL)-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Health Utility Score
timeFrame: Baseline and time of last PRO assessment (up to ~5 years)
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center ( Site 0026)
state: Arizona
city: Tucson
country: United States
facility: The University of Arizona Cancer Center - North Campus ( Site 0039)
state: Arizona
city: Duarte
country: United States
facility: City of Hope Medical Center ( Site 0027)
state: California
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale New Haven ( Site 0042)
state: Connecticut
city: Fort Myers
country: United States
facility: Regional Cancer Center ( Site 0054)
state: Florida
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center ( Site 0075)
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa ( Site 0067)
state: Iowa
city: Louisville
country: United States
facility: James Graham Brown Cancer Center ( Site 0088)
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville ( Site 0059)
state: Kentucky
city: New Orleans
country: United States
facility: University Medical Center New Orleans ( Site 0014)
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital ( Site 0062)
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center ( Site 0025)
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Ctr. ( Site 0033)
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Worcester ( Site 0017)
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital-GI/Hepatology Research ( Site 0047)
state: Michigan
city: Albuquerque
country: United States
facility: University of New Mexico ( Site 0041)
state: New Mexico
city: Lake Success
country: United States
facility: North Shore-Long Island Jewish Health System ( Site 0068)
state: New York
city: Centerville
country: United States
facility: Miami Valley Hospital South ( Site 0093)
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center ( Site 0084)
state: Ohio
city: Sylvania
country: United States
facility: ProMedica Flower Hospital ( Site 0090)
state: Ohio
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center ( Site 0045)
state: Oklahoma
city: Nashville
country: United States
facility: Vanderbilt Ingram Cancer Center ( Site 0006)
state: Tennessee
city: Temple
country: United States
facility: Baylor Scott & White Medical Center - Temple ( Site 0089)
state: Texas
city: Seattle
country: United States
facility: Virginia Mason Medical Center ( Site 0028)
state: Washington
city: Pilar
country: Argentina
facility: Hospital Universitario Austral ( Site 0795)
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Fundación favaloro para la Docencia e Investigación Médica ( Site 0808)
state: Caba
city: Rosario
country: Argentina
facility: Hospital Provincial del Centenario ( Site 0794)
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Hospital Aleman ( Site 0806)
city: Buenos Aires
country: Argentina
facility: Hospital Italiano ( Site 0793)
city: Buenos Aires
country: Argentina
facility: Hospital Britanico de Buenos Aires ( Site 0792)
city: Santa Fe
country: Argentina
facility: Clinica de nefrologia urologia y enfermedades cardiovasculares ( Site 0802)
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital AW ( Site 0225)
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital ( Site 0226)
state: New South Wales
city: Woollongabba
country: Australia
facility: Princess Alexandra Hospital ( Site 0228)
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital ( Site 0234)
state: South Australia
city: Clayton
country: Australia
facility: Monash Health ( Site 0233)
state: Victoria
city: Fitzroy
country: Australia
facility: St Vincents Hospital Melbourne ( Site 0227)
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Health ( Site 0230)
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital ( Site 0229)
state: Western Australia
city: Edegem
country: Belgium
facility: University Hospital Antwerp (UZA) ( Site 0374)
state: Antwerpen
city: Bruxelles
country: Belgium
facility: Erasme Hospital ( Site 0376)
state: Bruxelles-Capitale, Region De
city: Gent
country: Belgium
facility: UZ Gent ( Site 0375)
state: Oost-Vlaanderen
city: Leuven
country: Belgium
facility: UZ Leuven ( Site 0377)
state: Vlaams-Brabant
city: Curitiba
country: Brazil
facility: CIONC - Centro Integrado de Oncologia de Curitiba ( Site 0813)
state: Parana
city: Recife
country: Brazil
facility: Hospital de Cancer de Pernambuco ( Site 0815)
state: Pernambuco
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre ( Site 0824)
state: Rio Grande Do Sul
city: Blumenau
country: Brazil
facility: Clinica de Oncologia Reichow ( Site 0818)
state: Santa Catarina
city: Itajai
country: Brazil
facility: Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral ( Site 0820)
state: Santa Catarina
city: São Paulo
country: Brazil
facility: Hospital Paulistano ( Site 0829)
state: Sao Paulo
city: Rio de Janeiro
country: Brazil
facility: Instituto COI de Pesquisa Educacao e Gestao ( Site 0825)
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0826)
city: Sao Paulo
country: Brazil
facility: Real e Benemerita Associacao Portuguesa de Beneficencia ( Site 0828)
city: Sao Paulo
country: Brazil
facility: A.C. Camargo Cancer Center ( Site 0827)
city: Sao Paulo
country: Brazil
facility: Casa de Saude Santa Marcelina ( Site 0821)
city: Plovdiv
country: Bulgaria
facility: Complex Cancer Center Plovdiv-First Medical Oncology Department ( Site 0982)
city: Halifax
country: Canada
facility: Nova Scotia Health Authority QEII-HSC ( Site 0208)
state: Nova Scotia
city: Montreal
country: Canada
facility: Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0211)
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre ( Site 0207)
state: Quebec
city: Hefei
country: China
facility: Anhui Provincil Hospital South District ( Site 0181)
state: Anhui
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences ( Site 0156)
state: Beijing
city: Beijing
country: China
facility: Peking University People's Hospital ( Site 0191)
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital ( Site 0155)
state: Beijing
city: Fuzhou
country: China
facility: Fujian Provincial Cancer Hospital ( Site 0165)
state: Fujian
city: Fuzhou
country: China
facility: 900 Hospital of the Joint ( Site 0197)
state: Fujian
city: Guangzhou
country: China
facility: Guangdong General Hospital ( Site 0166)
state: Guangdong
city: Guangzhou
country: China
facility: Southern Medical University Nanfang Hospital ( Site 0172)
state: Guangdong
city: Wuhan
country: China
facility: Wuhan Union Hospital ( Site 0173)
state: Hubei
city: Wuhan
country: China
facility: Hubei Cancer Hospital ( Site 0189)
state: Hubei
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University ( Site 0167)
state: Hunan
city: Changsha
country: China
facility: Hunan Provincial People Hospital ( Site 0192)
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hospital ( Site 0168)
state: Hunan
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center ( Site 0161)
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University ( Site 0193)
state: Shanghai
city: Shanghai
country: China
facility: Renji Hospital Shanghai Jiaotong University School of Medicine ( Site 0174)
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital affiliated to Fudan University ( Site 0153)
state: Shanghai
city: XI An
country: China
facility: The First Affiliated Hospital of Xi an Jiaotong University ( Site 0164)
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital of Sichuan University ( Site 0162)
state: Sichuan
city: Urumqi
country: China
facility: Affiliated Tumor Hospital of Xinjiang Medical University ( Site 0157)
state: Xinjiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital ( Site 0171)
state: Zhejiang
city: Herlev
country: Denmark
facility: Herlev Hospital ( Site 0421)
state: Hovedstaden
city: Aarhus N
country: Denmark
facility: Aarhus Universitets hospital ( Site 0420)
state: Midtjylland
city: Odense C
country: Denmark
facility: Odense Universitets Hospital ( Site 0422)
state: Syddanmark
city: Strasbourg
country: France
facility: HUS Hopital Hautepierre ( Site 0445)
state: Bas-Rhin
city: Marseille
country: France
facility: Hopital de la Timone ( Site 0442)
state: Bouches-du-Rhone
city: Pessac
country: France
facility: CHU Bordeaux Haut-Leveque ( Site 0437)
state: Gironde
city: Toulouse
country: France
facility: CHU Rangueil ( Site 0441)
state: Haute-Garonne
city: Clichy
country: France
facility: Hopital Beaujon ( Site 0439)
state: Hauts-de-Seine
city: Montpellier
country: France
facility: CHU Montpellier. ( Site 0443)
state: Herault
city: Lille
country: France
facility: Hopital Claude Huriez CHRU LILLE ( Site 0440)
state: Nord
city: Villejuif
country: France
facility: Hopital Paul Brousse ( Site 0447)
state: Val-de-Marne
city: Heilbronn
country: Germany
facility: SLK-Kliniken Heilbronn GmbH ( Site 0460)
state: Baden-Wurttemberg
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen ( Site 0466)
state: Baden-Wurttemberg
city: Muenchen
country: Germany
facility: Klinikum rechts der Isar der Technischen Universitaet ( Site 0470)
state: Bayern
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg ( Site 0468)
state: Bayern
city: Frankfurt am Main
country: Germany
facility: Krankenhaus Nord-West GmbH ( Site 0472)
state: Hessen
city: Frankfurt
country: Germany
facility: Universitaetsklinikum Frankfurt ( Site 0467)
state: Hessen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover ( Site 0458)
state: Niedersachsen
city: Duesseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf ( Site 0461)
state: Nordrhein-Westfalen
city: Koeln
country: Germany
facility: Universitaetsklinikum Koeln ( Site 0463)
state: Nordrhein-Westfalen
city: Dresden
country: Germany
facility: Staedtisches Klinikum Dresden ( Site 0471)
state: Sachsen
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus ( Site 0459)
state: Sachsen
city: Berlin
country: Germany
facility: Charite - Campus Virchow Klinikum ( Site 0457)
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf ( Site 0469)
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital ( Site 0268)
city: Hong Kong
country: Hong Kong
facility: Pamela Youde Nethersole Eastern Hospital ( Site 0271)
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital ( Site 0267)
city: Tuen Mun
country: Hong Kong
facility: Tuen Mun Hospital ( Site 0272)
city: Kecskemét
country: Hungary
facility: Bacs-Kiskun Megyei Korhaz-Onkoradiologiai Kozpont ( Site 0483)
state: Bacs-Kiskun
city: Szeged
country: Hungary
facility: SZTE Szent-Gyorgyi Albert Klinikai Kozpont ( Site 0482)
state: Csongrad
city: Kaposvár
country: Hungary
facility: Somogy Megyei Kaposi Mór Oktató Kórház-Oncology center ( Site 0484)
state: Somogy
city: Budapest
country: Hungary
facility: Semmelweis University ( Site 0480)
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont Onkologiai Tanszek ( Site 0481)
city: Dublin
country: Ireland
facility: St Vincent's University Hospital ( Site 0498)
city: Dublin
country: Ireland
facility: Tallaght University Hospital ( Site 0499)
city: Haifa
country: Israel
facility: Rambam Medical Center ( Site 0524)
city: Jerusalem
country: Israel
facility: Haddassah Medical Organization - Ein Kerem ( Site 0519)
city: Petah Tikva
country: Israel
facility: Rabin Medical Center ( Site 0520)
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center ( Site 0523)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 0522)
city: Modena
country: Italy
facility: A O U Policlinico di Modena ( Site 0548)
state: Abruzzo
city: Torino
country: Italy
facility: Azienda Ospedaliera Ordine Mauriziano di Torino ( Site 0542)
state: Piemonte
city: Palermo
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello ( Site 0547)
state: Sicilia
city: Bari
country: Italy
facility: Istituto Tumori Giovanni Paolo II ( Site 0543)
city: Bologna
country: Italy
facility: AOU di Bologna Policliico S. Orsola-Malpighi ( Site 0541)
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi ( Site 0549)
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico ( Site 0550)
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0540)
city: Napoli
country: Italy
facility: Ospedale del Mare ( Site 0545)
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana ( Site 0546)
city: Toon
country: Japan
facility: Ehime University Hospital ( Site 0123)
state: Ehime
city: Kurume
country: Japan
facility: Kurume University Hospital ( Site 0119)
state: Fukuoka
city: Sapporo
country: Japan
facility: Hokkaido P.W.F.A.C Sapporo-Kosei General Hospital ( Site 0102)
state: Hokkaido
city: Kanazawa
country: Japan
facility: Kanazawa University Hospital ( Site 0111)
state: Ishikawa
city: Kita-gun
country: Japan
facility: Kagawa University Hospital ( Site 0121)
state: Kagawa
city: Takamatsu
country: Japan
facility: Kagawa Prefectural Central Hospital ( Site 0122)
state: Kagawa
city: Kawasaki
country: Japan
facility: Toranomon Hospital Kajigaya ( Site 0109)
state: Kanagawa
city: Yokohama
country: Japan
facility: Yokohama City University Medical Center ( Site 0110)
state: Kanagawa
city: Osakasayama
country: Japan
facility: Kindai University Hospital ( Site 0116)
state: Osaka
city: Iruma-gun
country: Japan
facility: Saitama Medical University Hospital ( Site 0104)
state: Saitama
city: Mitaka
country: Japan
facility: Kyorin University Hospital ( Site 0106)
state: Tokyo
city: Musashino
country: Japan
facility: Musashino Red Cross Hospital ( Site 0107)
state: Tokyo
city: Chiba
country: Japan
facility: Chiba University Hospital ( Site 0103)
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Medical Center ( Site 0118)
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital ( Site 0117)
city: Kyoto
country: Japan
facility: University Hospital, Kyoto Prefectural University of Medicine ( Site 0112)
city: Osaka
country: Japan
facility: Japanese Red Cross Osaka Hospital ( Site 0113)
city: Osaka
country: Japan
facility: Osaka Metropolitan University Hospital. ( Site 0114)
city: Saga
country: Japan
facility: Saga-Ken Medical Centre Koseikan ( Site 0120)
city: Tokyo
country: Japan
facility: Toranomon Hospital ( Site 0108)
city: Tokyo
country: Japan
facility: The University of Tokyo Hospital ( Site 0105)
city: Wakayama
country: Japan
facility: Wakayama Medical University Hospital ( Site 0115)
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center ( Site 0314)
state: Kyonggi-do
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital ( Site 0313)
state: Kyonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 0312)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System ( Site 0309)
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center ( Site 0310)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center ( Site 0311)
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea. Seoul St. Mary s Hospital ( Site 0315)
city: Kubang Kerian
country: Malaysia
facility: Hospital Universiti Sains Malaysia ( Site 0295)
state: Kelantan
city: George Town
country: Malaysia
facility: Penang Adventist Hospital ( Site 0289)
state: Pulau Pinang
city: Penang
country: Malaysia
facility: Gleneagles Penang ( Site 0290)
state: Pulau Pinang
city: Kuching
country: Malaysia
facility: Sarawak General Hospital ( Site 0293)
state: Sarawak
city: Putrajaya Wilayah Persekutuan
country: Malaysia
facility: Institut Kanser Negara - National Cancer Institute ( Site 0294)
state: Wilayah Persekutuan Putrajaya
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre ( Site 0288)
city: Christchurch
country: New Zealand
facility: Christchurch Hospital ( Site 0247)
state: Canterbury
city: Auckland
country: New Zealand
facility: Auckland City Hospital ( Site 0246)
city: Oslo
country: Norway
facility: Oslo Universitetssykehus HF. Ulleval ( Site 0433)
city: Szklarska Poreba
country: Poland
facility: Izerskie Centrum Pulmonologii i Chemioterapii IZER-MED Spolka z o.o. ( Site 0607)
state: Dolnoslaskie
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie ( Site 0620)
state: Lubelskie
city: Warsaw
country: Poland
facility: MTZ Clinical Research Sp. z o. o. ( Site 0608)
state: Mazowieckie
city: Gdansk
country: Poland
facility: Copernicus PL Sp. z o.o. ( Site 0603)
state: Pomorskie
city: Myslowice
country: Poland
facility: ID Clinic ( Site 0619)
state: Slaskie
city: Olsztyn
country: Poland
facility: SPZOZ MSWIA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie ( Site 0606)
state: Warminsko-mazurskie
city: Koszalin
country: Poland
facility: Szpital Wojewodzki im. Mikolaja Kopernika ( Site 0604)
state: Zachodniopomorskie
city: Barnaul
country: Russian Federation
facility: Altay Regional Oncology Dispensary ( Site 0919)
state: Altayskiy Kray
city: Krasnoyarsk
country: Russian Federation
facility: Siberian Clinical Center of FMBA ( Site 0918)
state: Krasnoyarskiy Kray
city: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0648)
state: Krasnoyarskiy Kray
city: Moscow
country: Russian Federation
facility: Blokhin National Medical Oncology ( Site 0645)
state: Moskva
city: Moscow
country: Russian Federation
facility: City Clinical Hospital 1 na. NI. Pirogov ( Site 0662)
state: Moskva
city: Moscow
country: Russian Federation
facility: First Moscow State Medical University n.a. I.M.Sechenov ( Site 0661)
state: Moskva
city: Moscow
country: Russian Federation
facility: Hadassah Medical-Clinical Research Department ( Site 0920)
state: Moskva
city: Moscow
country: Russian Federation
facility: National Medical Research Radiological Centre ( Site 0660)
state: Moskva
city: Nizhniy Novgorod
country: Russian Federation
facility: Privolzhsky District Medical Center ( Site 0655)
state: Nizhegorodskaya Oblast
city: Samara
country: Russian Federation
facility: Samara Regional Clinical Oncology Center ( Site 0656)
state: Samarskaya Oblast
city: Saint Petersburg
country: Russian Federation
facility: Road Hospital JSC Russian railways ( Site 0649)
state: Sankt-Peterburg
city: Saint Petersburg
country: Russian Federation
facility: Russian Scientific Center of Radiology and Surgical Technologies ( Site 0665)
state: Sankt-Peterburg
city: Saint Petersburg
country: Russian Federation
facility: City Clinical Oncology Center ( Site 0646)
state: Sankt-Peterburg
city: Tomsk
country: Russian Federation
facility: Tomsk Scientific Research Institute of Oncology ( Site 0657)
state: Tomskaya Oblast
city: Oviedo
country: Spain
facility: Hospital Central de Asturias ( Site 0667)
state: Asturias
city: Sabadell
country: Spain
facility: Hospital Universitari Parc Tauli ( Site 0681)
state: Barcelona
city: San Sebastian
country: Spain
facility: Hospital Universitario de Donostia ( Site 0671)
state: Gipuzkoa
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago ( Site 0668)
state: La Coruna
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro ( Site 0678)
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d Hebron ( Site 0674)
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon ( Site 0676)
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal ( Site 0673)
city: Madrid
country: Spain
facility: Hospital Universitario La Paz ( Site 0677)
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio ( Site 0670)
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet-Gastroenterology ( Site 0682)
city: Malmo
country: Sweden
facility: Skane University Hospital ( Site 0692)
state: Skane Lan
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset, Huddinge ( Site 0689)
state: Stockholms Lan
city: Umea
country: Sweden
facility: Norrlands Universitetssjukhus ( Site 0687)
state: Vasterbottens Lan
city: Goteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset ( Site 0691)
state: Vastra Gotalands Lan
city: Bern
country: Switzerland
facility: Universitaetsspital Bern ( Site 0710)
state: Aargau
city: Basel
country: Switzerland
facility: University Hospital Basel ( Site 0709)
state: Basel-Stadt
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen ( Site 0708)
state: Sankt Gallen
city: Lausanne
country: Switzerland
facility: CHUV (centre hospitalier universitaire vaudois) ( Site 0712)
state: Vaud
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur ( Site 0714)
state: Zurich
city: Geneve
country: Switzerland
facility: Hopitaux Universitaires de Geneve HUG ( Site 0711)
city: Zurich
country: Switzerland
facility: Universitaetsspital Zurich ( Site 0713)
city: Kaohsiung
country: Taiwan
facility: Chang Gung Medical Foundation. Kaohsiung Branch ( Site 0335)
city: Taichung
country: Taiwan
facility: China Medical University Hospital ( Site 0333)
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital ( Site 0334)
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital ( Site 0330)
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital ( Site 0331)
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation. Linkou ( Site 0332)
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital. ( Site 0352)
state: Krung Thep Maha Nakhon
city: Bangkok
country: Thailand
facility: Siriraj Hospital ( Site 0351)
state: Krung Thep Maha Nakhon
city: Chiang Mai
country: Thailand
facility: Maharaj Nakorn Chiangmai Hospital ( Site 0353)
city: Khon Kaen
country: Thailand
facility: Srinagarind Hospital ( Site 0354)
city: Tekirdag
country: Turkey
facility: Namik Kemal Universitesi Tip Fakultesi ( Site 0738)
state: Tekirdas
city: Adana
country: Turkey
facility: Baskent Unv. Adana Uyg. ve Arast. Hastanesi ( Site 0733)
city: Ankara
country: Turkey
facility: Gulhane Egitim ve Arastirma Hastanesi ( Site 0741)
city: Ankara
country: Turkey
facility: Ankara Sehir Hastanesi ( Site 0731)
city: Aydin
country: Turkey
facility: Adnan Menderes University Medical Faculty ( Site 0737)
city: Istanbul
country: Turkey
facility: Bezmialem Vakif University School of Medicine ( Site 0732)
city: Istanbul
country: Turkey
facility: Acıbadem Maslak Hastanesi ( Site 0742)
city: Istanbul
country: Turkey
facility: Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 0730)
city: Izmir
country: Turkey
facility: Dokuz Eylul Universitesi ( Site 0740)
city: Konya
country: Turkey
facility: Konya Necmettin Erbakan University Medical Faculty ( Site 0736)
city: Malatya
country: Turkey
facility: Inonu University Faculty of Medicine ( Site 0729)
city: Mersin
country: Turkey
facility: VM Medical Park Hastanesi ( Site 0739)
city: Chernivtsi
country: Ukraine
facility: Regional Clinical Onco Dispensary_ State Medical University ( Site 0782)
state: Chernivetska Oblast
city: Kharkiv
country: Ukraine
facility: Regional Oncology Center of Kharkiv ( Site 0777)
state: Kharkivska Oblast
city: Kyiv
country: Ukraine
facility: National Cancer Institute of the MoH of Ukraine ( Site 0779)
state: Kyivska Oblast
city: Kyiv
country: Ukraine
facility: Shalimov s NI of Surgery and Transplantation ( Site 0781)
state: Kyivska Oblast
city: Odesa
country: Ukraine
facility: MI Odessa Regional Oncological Centre ( Site 0776)
state: Odeska Oblast
city: Zaporizhzhia
country: Ukraine
facility: CI City Clinical Hospital # 3 ( Site 0783)
state: Zaporizka Oblast
city: Kyiv
country: Ukraine
facility: Universal Clinic Oberig-Oncology Center ( Site 0786)
city: Kyiv
country: Ukraine
facility: Medical Center Dobrobut Clinic ( Site 0785)
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Trust ( Site 0755)
state: Cambridgeshire
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital ( Site 0753)
state: Derbyshire
city: Glasgow
country: United Kingdom
facility: The Beatson West of Scotland Cancer Centre ( Site 0750)
state: Glasgow City
city: London
country: United Kingdom
facility: Kings College Hospital NHS Foundation Trust ( Site 0758)
state: London, City Of
city: Belfast
country: United Kingdom
facility: Belfast City Hospital ( Site 0752)
state: Northern Ireland
city: Birkenhead
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust ( Site 0757)
state: Wirral
city: Coventry
country: United Kingdom
facility: University Hospital Coventry and Warwickshire NHS Trust ( Site 0754)
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust ( Site 0751)
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust ( Site 0756)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Verset G, Borbath I, Karwal M, Verslype C, Van Vlierberghe H, Kardosh A, Zagonel V, Stal P, Sarker D, Palmer DH, Vogel A, Edeline J, Cattan S, Kudo M, Cheng AL, Ogasawara S, Daniele B, Chan SL, Knox JJ, Qin S, Siegel AB, Chisamore M, Hatogai K, Wang A, Finn RS, Zhu AX. Pembrolizumab Monotherapy for Previously Untreated Advanced Hepatocellular Carcinoma: Data from the Open-Label, Phase II KEYNOTE-224 Trial. Clin Cancer Res. 2022 Jun 13;28(12):2547-2554. doi: 10.1158/1078-0432.CCR-21-3807.