AzTrials
AzTrials

Hepatocellular CarcinomaPhase 3NCT03867084

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)

A Phase 3 study testing Pembrolizumab in people with Hepatocellular Carcinoma, run by Merck Sharp & Dohme LLC at 249 sites in 31 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatocellular Carcinoma
What is being tested?
Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
959 participants
Where
249 sitesin 31 countries
Study dates
28 May 2019to 30 Sep 2025
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

249 sites in 31 countries.

249 sites in 31 countries

United States24 sites

  • University of New Mexico ( Site 0041)

    Albuquerque, New Mexico, 87131

  • Massachusetts General Hospital ( Site 0062)

    Boston, Massachusetts, 02114

  • Boston Medical Center ( Site 0025)

    Boston, Massachusetts, 02118

  • Beth Israel Deaconess Medical Ctr. ( Site 0033)

    Boston, Massachusetts, 02215

  • Miami Valley Hospital South ( Site 0093)

    Centerville, Ohio, 45459

  • University of Cincinnati Medical Center ( Site 0084)

    Cincinnati, Ohio, 45219

  • Henry Ford Hospital-GI/Hepatology Research ( Site 0047)

    Detroit, Michigan, 48202

  • City of Hope Medical Center ( Site 0027)

    Duarte, California, 91010

  • Regional Cancer Center ( Site 0054)

    Fort Myers, Florida, 33905

  • Banner MD Anderson Cancer Center ( Site 0026)

    Gilbert, Arizona, 85234

  • Indiana University Simon Cancer Center ( Site 0075)

    Indianapolis, Indiana, 46202

  • University of Iowa ( Site 0067)

    Iowa City, Iowa, 52242

  • North Shore-Long Island Jewish Health System ( Site 0068)

    Lake Success, New York, 11042

  • James Graham Brown Cancer Center ( Site 0088)

    Louisville, Kentucky, 40202

  • University of Louisville ( Site 0059)

    Louisville, Kentucky, 40202

  • Vanderbilt Ingram Cancer Center ( Site 0006)

    Nashville, Tennessee, 37232

  • Smilow Cancer Hospital at Yale New Haven ( Site 0042)

    New Haven, Connecticut, 06510

  • University Medical Center New Orleans ( Site 0014)

    New Orleans, Louisiana, 70112

  • Stephenson Cancer Center ( Site 0045)

    Oklahoma City, Oklahoma, 73104

  • Virginia Mason Medical Center ( Site 0028)

    Seattle, Washington, 98101

  • ProMedica Flower Hospital ( Site 0090)

    Sylvania, Ohio, 43560

  • Baylor Scott & White Medical Center - Temple ( Site 0089)

    Temple, Texas, 76508

  • The University of Arizona Cancer Center - North Campus ( Site 0039)

    Tucson, Arizona, 85719

  • University of Massachusetts Worcester ( Site 0017)

    Worcester, Massachusetts, 01655

Other trials in United States

Japan22 sites

  • Chiba University Hospital ( Site 0103)

    Chiba, 260-8677

  • National Hospital Organization Kyushu Medical Center ( Site 0118)

    Fukuoka, 810-8563

  • Hiroshima University Hospital ( Site 0117)

    Hiroshima, 7348551

  • Saitama Medical University Hospital ( Site 0104)

    Iruma-gun, Saitama, 350-0495

  • Kanazawa University Hospital ( Site 0111)

    Kanazawa, Ishikawa-ken, 920-8641

  • Toranomon Hospital Kajigaya ( Site 0109)

    Kawasaki, Kanagawa, 213-8587

  • Kagawa University Hospital ( Site 0121)

    Kita-gun, Kagawa-ken, 761-0793

  • Kurume University Hospital ( Site 0119)

    Kurume, Fukuoka, 830-0011

  • University Hospital, Kyoto Prefectural University of Medicine ( Site 0112)

    Kyoto, 602-8566

  • Kyorin University Hospital ( Site 0106)

    Mitaka, Tokyo, 181-8611

  • Musashino Red Cross Hospital ( Site 0107)

    Musashino, Tokyo, 180-8610

  • Japanese Red Cross Osaka Hospital ( Site 0113)

    Osaka, 543-8555

  • Osaka Metropolitan University Hospital. ( Site 0114)

    Osaka, 545-8586

  • Saga-Ken Medical Centre Koseikan ( Site 0120)

    Saga, 840-8571

  • Hokkaido P.W.F.A.C Sapporo-Kosei General Hospital ( Site 0102)

    Sapporo, Hokkaido, 060-0033

  • Kindai University Hospital ( Site 0116)

    Sayama, Osaka, 5898511

  • Kagawa Prefectural Central Hospital ( Site 0122)

    Takamatsu, Kagawa-ken, 760-8557

  • Toranomon Hospital ( Site 0108)

    Tokyo, 105-8470

  • The University of Tokyo Hospital ( Site 0105)

    Tokyo, 113-8655

  • Ehime University Hospital ( Site 0123)

    Tōon, Ehime, 791-0295

  • Wakayama Medical University Hospital ( Site 0115)

    Wakayama, 641-8510

  • Yokohama City University Medical Center ( Site 0110)

    Yokohama, Kanagawa, 232-0024

Other trials in Japan

China21 sites

  • Cancer Hospital Chinese Academy of Medical Sciences ( Site 0156)

    Beijing, Beijing Municipality, 100021

  • Peking University People's Hospital ( Site 0191)

    Beijing, Beijing Municipality, 100044

  • Beijing Cancer Hospital ( Site 0155)

    Beijing, Beijing Municipality, 100142

  • The Third Xiangya Hospital of Central South University ( Site 0167)

    Changsha, Hunan, 410000

  • Hunan Provincial People Hospital ( Site 0192)

    Changsha, Hunan, 410005

  • Hunan Cancer Hospital ( Site 0168)

    Changsha, Hunan, 410013

  • West China Hospital of Sichuan University ( Site 0162)

    Chengdu, Sichuan, 610041

  • Fujian Provincial Cancer Hospital ( Site 0165)

    Fuzhou, Fujian, 350014

  • 900 Hospital of the Joint ( Site 0197)

    Fuzhou, Fujian, 350025

  • Guangdong General Hospital ( Site 0166)

    Guangzhou, Guangdong, 510080

  • Southern Medical University Nanfang Hospital ( Site 0172)

    Guangzhou, Guangdong, 510515

  • Zhejiang Cancer Hospital ( Site 0171)

    Hangzhou, Zhejiang, 310022

  • Anhui Provincil Hospital South District ( Site 0181)

    Hefei, Anhui, 230036

  • Fudan University Shanghai Cancer Center ( Site 0161)

    Shanghai, Shanghai Municipality, 200032

  • Zhongshan Hospital Fudan University ( Site 0193)

    Shanghai, Shanghai Municipality, 200032

  • Renji Hospital Shanghai Jiaotong University School of Medicine ( Site 0174)

    Shanghai, Shanghai Municipality, 200127

  • Zhongshan Hospital affiliated to Fudan University ( Site 0153)

    Shanghai, Shanghai Municipality, 210000

  • Affiliated Tumor Hospital of Xinjiang Medical University ( Site 0157)

    Ürümqi, Xinjiang, 830001

  • Wuhan Union Hospital ( Site 0173)

    Wuhan, Hubei, 430022

  • Hubei Cancer Hospital ( Site 0189)

    Wuhan, Hubei, 430079

  • The First Affiliated Hospital of Xi an Jiaotong University ( Site 0164)

    Xi’an, Shanxi, 710061

Other trials in China

Russia14 sites

  • Altay Regional Oncology Dispensary ( Site 0919)

    Barnaul, Altayskiy Kray, 656045

  • Siberian Clinical Center of FMBA ( Site 0918)

    Krasnoyarsk, Krasnoyarsk Krai, 660037

  • Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0648)

    Krasnoyarsk, Krasnoyarsk Krai, 660133

  • Blokhin National Medical Oncology ( Site 0645)

    Moscow, Moscow, 115478

  • City Clinical Hospital 1 na. NI. Pirogov ( Site 0662)

    Moscow, Moscow, 119049

  • First Moscow State Medical University n.a. I.M.Sechenov ( Site 0661)

    Moscow, Moscow, 119881

  • Hadassah Medical-Clinical Research Department ( Site 0920)

    Moscow, Moscow, 121205

  • National Medical Research Radiological Centre ( Site 0660)

    Moscow, Moscow, 125284

  • Privolzhsky District Medical Center ( Site 0655)

    Nizhny Novgorod, Nizhny Novgorod Oblast, 603109

  • Road Hospital JSC Russian railways ( Site 0649)

    Saint Petersburg, Sankt-Peterburg, 195271

  • Russian Scientific Center of Radiology and Surgical Technologies ( Site 0665)

    Saint Petersburg, Sankt-Peterburg, 197758

  • City Clinical Oncology Center ( Site 0646)

    Saint Petersburg, Sankt-Peterburg, 198255

  • Samara Regional Clinical Oncology Center ( Site 0656)

    Samara, Samara Oblast, 443031

  • Tomsk Scientific Research Institute of Oncology ( Site 0657)

    Tomsk, Tomsk Oblast, 634028

Other trials in Russia

Germany13 sites

  • Charite - Campus Virchow Klinikum ( Site 0457)

    Berlin, 13353

  • Universitaetsklinikum Koeln ( Site 0463)

    Cologne, North Rhine-Westphalia, 50937

  • Staedtisches Klinikum Dresden ( Site 0471)

    Dresden, Saxony, 01067

  • Universitatsklinikum Carl Gustav Carus ( Site 0459)

    Dresden, Saxony, 01307

  • Universitaetsklinikum Duesseldorf ( Site 0461)

    Düsseldorf, North Rhine-Westphalia, 40225

  • Krankenhaus Nord-West GmbH ( Site 0472)

    Frankfurt am Main, Hesse, 60488

  • Universitaetsklinikum Frankfurt ( Site 0467)

    Frankfurt am Main, Hesse, 60596

  • Universitaetsklinikum Hamburg-Eppendorf ( Site 0469)

    Hamburg, 20246

  • Medizinische Hochschule Hannover ( Site 0458)

    Hanover, Lower Saxony, 30625

  • SLK-Kliniken Heilbronn GmbH ( Site 0460)

    Heilbronn, Baden-Wurttemberg, 74078

  • Klinikum rechts der Isar der Technischen Universitaet ( Site 0470)

    Munich, Bavaria, 81675

  • Universitaetsklinikum Tuebingen ( Site 0466)

    Tübingen, Baden-Wurttemberg, 72076

  • Universitaetsklinikum Wuerzburg ( Site 0468)

    Würzburg, Bavaria, 97080

Other trials in Germany

Turkey (Türkiye)12 sites

  • Baskent Unv. Adana Uyg. ve Arast. Hastanesi ( Site 0733)

    Adana, 01120

  • Gulhane Egitim ve Arastirma Hastanesi ( Site 0741)

    Ankara, 06010

  • Ankara Sehir Hastanesi ( Site 0731)

    Ankara, 06800

  • Adnan Menderes University Medical Faculty ( Site 0737)

    Aydin, 09010

  • Bezmialem Vakif University School of Medicine ( Site 0732)

    Istanbul, 34093

  • Acıbadem Maslak Hastanesi ( Site 0742)

    Istanbul, 34457

  • Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 0730)

    Istanbul, 34722

  • Dokuz Eylul Universitesi ( Site 0740)

    Izmir, 35340

  • Konya Necmettin Erbakan University Medical Faculty ( Site 0736)

    Konya, 42080

  • Inonu University Faculty of Medicine ( Site 0729)

    Malatya, 44280

  • VM Medical Park Hastanesi ( Site 0739)

    Mersin, 33440

  • Namik Kemal Universitesi Tip Fakultesi ( Site 0738)

    Tekirdağ, Tekirdas, 59100

Other trials in Turkey (Türkiye)

Brazil11 sites

  • Clinica de Oncologia Reichow ( Site 0818)

    Blumenau, Santa Catarina, 89010-340

  • CIONC - Centro Integrado de Oncologia de Curitiba ( Site 0813)

    Curitiba, Paraná, 80810-050

  • Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral ( Site 0820)

    Itajaí, Santa Catarina, 88301-220

  • Hospital de Clinicas de Porto Alegre ( Site 0824)

    Porto Alegre, Rio Grande do Sul, 90035-903

  • Hospital de Cancer de Pernambuco ( Site 0815)

    Recife, Pernambuco, 50040-000

  • Instituto COI de Pesquisa Educacao e Gestao ( Site 0825)

    Rio de Janeiro, 22793-080

  • Hospital Paulistano ( Site 0829)

    São Paulo, São Paulo, 01321-001

  • Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0826)

    São Paulo, 01246-000

  • Real e Benemerita Associacao Portuguesa de Beneficencia ( Site 0828)

    São Paulo, 01321-001

  • A.C. Camargo Cancer Center ( Site 0827)

    São Paulo, 01509-900

  • Casa de Saude Santa Marcelina ( Site 0821)

    São Paulo, 08270120

Other trials in Brazil

Spain11 sites

  • Hospital Universitari Vall d Hebron ( Site 0674)

    Barcelona, 08035

  • Hospital Universitario de Donostia ( Site 0671)

    Donostia / San Sebastian, Gipuzkoa, 20014

  • Hospital General Universitario Gregorio Maranon ( Site 0676)

    Madrid, 28007

  • Hospital Ramon y Cajal ( Site 0673)

    Madrid, 28034

  • Hospital Universitario La Paz ( Site 0677)

    Madrid, 28046

  • Hospital Universitario Puerta de Hierro ( Site 0678)

    Majadahonda, Madrid, 28222

  • Hospital Central de Asturias ( Site 0667)

    Oviedo, Principality of Asturias, 33011

  • Hospital Universitari Parc Tauli ( Site 0681)

    Sabadell, Barcelona, 08208

  • Complejo Hospitalario Universitario de Santiago ( Site 0668)

    Santiago de Compostela, La Coruna, 15706

  • Hospital Universitario Virgen del Rocio ( Site 0670)

    Seville, 41013

  • Hospital Universitario Miguel Servet-Gastroenterology ( Site 0682)

    Zaragoza, 50009

Other trials in Spain

Italy10 sites

  • Istituto Tumori Giovanni Paolo II ( Site 0543)

    Bari, 70124

  • AOU di Bologna Policliico S. Orsola-Malpighi ( Site 0541)

    Bologna, 40138

  • Azienda Ospedaliero Universitaria Careggi ( Site 0549)

    Florence, 50134

  • Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico ( Site 0550)

    Milan, 20122

  • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0540)

    Milan, 20133

  • A O U Policlinico di Modena ( Site 0548)

    Modena, Abruzzo, 41025

  • Ospedale del Mare ( Site 0545)

    Naples, 80147

  • Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello ( Site 0547)

    Palermo, Sicily, 90146

  • Azienda Ospedaliero Universitaria Pisana ( Site 0546)

    Pisa, 56126

  • Azienda Ospedaliera Ordine Mauriziano di Torino ( Site 0542)

    Turin, Piedmont

Other trials in Italy

United Kingdom9 sites

  • Belfast City Hospital ( Site 0752)

    Belfast, Northern Ireland, BT9 7AB

  • The Clatterbridge Cancer Centre NHS Foundation Trust ( Site 0757)

    Birkenhead, Wirral, CH63 4JY

  • Cambridge University Hospitals NHS Trust ( Site 0755)

    Cambridge, Cambridgeshire, CB2 0QQ

  • University Hospital Coventry and Warwickshire NHS Trust ( Site 0754)

    Coventry, CV3 2DX

  • The Beatson West of Scotland Cancer Centre ( Site 0750)

    Glasgow, Glasgow City, G12 0YN

  • Leeds Teaching Hospitals NHS Trust ( Site 0751)

    Leeds, LS9 7TF

  • Kings College Hospital NHS Foundation Trust ( Site 0758)

    London, London, City of, SE5 9RS

  • Nottingham University Hospitals NHS Trust ( Site 0756)

    Nottingham, NG5 1PB

  • Weston Park Hospital ( Site 0753)

    Sheffield, Derbyshire, S10 2SJ

Other trials in United Kingdom

Australia8 sites

  • Royal Adelaide Hospital ( Site 0234)

    Adelaide, South Australia, 5000

  • Royal Prince Alfred Hospital AW ( Site 0225)

    Camperdown, New South Wales, 2050

  • Monash Health ( Site 0233)

    Clayton, Victoria, 3168

  • St Vincents Hospital Melbourne ( Site 0227)

    Fitzroy, Victoria, 3065

  • Liverpool Hospital ( Site 0226)

    Liverpool, New South Wales, 2170

  • Alfred Health ( Site 0230)

    Melbourne, Victoria, 3004

  • Royal Perth Hospital ( Site 0229)

    Perth, Western Australia, 6000

  • Princess Alexandra Hospital ( Site 0228)

    Woollongabba, Queensland, 4102

Other trials in Australia

France8 sites

  • Hopital Beaujon ( Site 0439)

    Clichy, Hauts-de-Seine, 92118

  • Hopital Claude Huriez CHRU LILLE ( Site 0440)

    Lille, Nord, 59037

  • Hopital de la Timone ( Site 0442)

    Marseille, Bouches-du-Rhone, 13005

  • CHU Montpellier. ( Site 0443)

    Montpellier, Herault, 34295

  • CHU Bordeaux Haut-Leveque ( Site 0437)

    Pessac, Gironde, 33604

  • HUS Hopital Hautepierre ( Site 0445)

    Strasbourg, Bas-Rhin, 67098

  • CHU Rangueil ( Site 0441)

    Toulouse, Haute-Garonne, 31059

  • Hopital Paul Brousse ( Site 0447)

    Villejuif, Val-de-Marne, 94800

Other trials in France

Ukraine8 sites

  • Regional Clinical Onco Dispensary_ State Medical University ( Site 0782)

    Chernivtsi, Chernivetska Oblast, 58000

  • Regional Oncology Center of Kharkiv ( Site 0777)

    Kharkiv, Kharkiv Oblast, 61000

  • National Cancer Institute of the MoH of Ukraine ( Site 0779)

    Kyiv, Kyivska Oblast, 03022

  • Shalimov s NI of Surgery and Transplantation ( Site 0781)

    Kyiv, Kyivska Oblast, 03126

  • Universal Clinic Oberig-Oncology Center ( Site 0786)

    Kyiv, 03057

  • Medical Center Dobrobut Clinic ( Site 0785)

    Kyiv, 03151

  • MI Odessa Regional Oncological Centre ( Site 0776)

    Odesa, Odesa Oblast, 65055

  • CI City Clinical Hospital # 3 ( Site 0783)

    Zaporizhzhya, Zaporizhzhia Oblast, 69032

Other trials in Ukraine

Argentina7 sites

  • Fundación favaloro para la Docencia e Investigación Médica ( Site 0808)

    Buenos Aires, Buenos Aires F.D., C1096AAS

  • Hospital Aleman ( Site 0806)

    Buenos Aires, C1118AAT

  • Hospital Italiano ( Site 0793)

    Buenos Aires, C1181ACH

  • Hospital Britanico de Buenos Aires ( Site 0792)

    Buenos Aires, C1280AEB

  • Hospital Universitario Austral ( Site 0795)

    Pilar, Buenos Aires, B1629AHJ

  • Hospital Provincial del Centenario ( Site 0794)

    Rosario, Santa Fe Province, S2002KDS

  • Clinica de nefrologia urologia y enfermedades cardiovasculares ( Site 0802)

    Santa Fe, S3000BPJ

Other trials in Argentina

Poland7 sites

  • Copernicus PL Sp. z o.o. ( Site 0603)

    Gdansk, Pomeranian Voivodeship, 80-219

  • Szpital Wojewodzki im. Mikolaja Kopernika ( Site 0604)

    Koszalin, West Pomeranian Voivodeship, 75-581

  • Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie ( Site 0620)

    Lublin, Lublin Voivodeship, 20-081

  • ID Clinic ( Site 0619)

    Mysłowice, Silesian Voivodeship, 41-400

  • SPZOZ MSWIA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie ( Site 0606)

    Olsztyn, Warmian-Masurian Voivodeship, 10-228

  • Izerskie Centrum Pulmonologii i Chemioterapii IZER-MED Spolka z o.o. ( Site 0607)

    Szklarska Poręba, Lower Silesian Voivodeship, 58-580

  • MTZ Clinical Research Sp. z o. o. ( Site 0608)

    Warsaw, Masovian Voivodeship, 02-106

Other trials in Poland

South Korea7 sites

  • National Cancer Center ( Site 0314)

    Goyang-si, Kyonggi-do, 10408

  • Seoul National University Bundang Hospital ( Site 0313)

    Seongnam-si, Kyonggi-do, 13605

  • Seoul National University Hospital ( Site 0312)

    Seoul, 03080

  • Severance Hospital Yonsei University Health System ( Site 0309)

    Seoul, 03722

  • Asan Medical Center ( Site 0310)

    Seoul, 05505

  • Samsung Medical Center ( Site 0311)

    Seoul, 06351

  • The Catholic University of Korea. Seoul St. Mary s Hospital ( Site 0315)

    Seoul, 06591

Other trials in South Korea

Switzerland7 sites

  • University Hospital Basel ( Site 0709)

    Basel, Canton of Basel-City, 4056

  • Universitaetsspital Bern ( Site 0710)

    Bern, Canton of Aargau, 3010

  • Hopitaux Universitaires de Geneve HUG ( Site 0711)

    Geneva, 1211

  • CHUV (centre hospitalier universitaire vaudois) ( Site 0712)

    Lausanne, Canton of Vaud, 1011

  • Kantonsspital St. Gallen ( Site 0708)

    Sankt Gallen, Canton of St. Gallen, 9007

  • Kantonsspital Winterthur ( Site 0714)

    Winterthur, Canton of Zurich, 8401

  • Universitaetsspital Zurich ( Site 0713)

    Zurich, 8091

Other trials in Switzerland

Malaysia6 sites

  • Gleneagles Penang ( Site 0290)

    George Town, Pulau Pinang, 10050

  • Penang Adventist Hospital ( Site 0289)

    George Town, Pulau Pinang, 10350

  • University Malaya Medical Centre ( Site 0288)

    Kuala Lumpur, 59100

  • Hospital Universiti Sains Malaysia ( Site 0295)

    Kubang Kerian, Kelantan, 16150

  • Sarawak General Hospital ( Site 0293)

    Kuching, Sarawak, 93586

  • Institut Kanser Negara - National Cancer Institute ( Site 0294)

    Putrajaya Wilayah Persekutuan, Putrajaya, 62250

Other trials in Malaysia

Taiwan6 sites

  • Chang Gung Medical Foundation. Kaohsiung Branch ( Site 0335)

    Kaohsiung City, 833

  • China Medical University Hospital ( Site 0333)

    Taichung, 40447

  • National Cheng Kung University Hospital ( Site 0334)

    Tainan, 704

  • National Taiwan University Hospital ( Site 0330)

    Taipei, 100

  • Taipei Veterans General Hospital ( Site 0331)

    Taipei, 112

  • Chang Gung Medical Foundation. Linkou ( Site 0332)

    Taoyuan, 333

Other trials in Taiwan

Hungary5 sites

  • Semmelweis University ( Site 0480)

    Budapest, 1085

  • Debreceni Egyetem Klinikai Kozpont Onkologiai Tanszek ( Site 0481)

    Debrecen, 4032

  • Somogy Megyei Kaposi Mór Oktató Kórház-Oncology center ( Site 0484)

    Kaposvár, Somogy County, 7400

  • Bacs-Kiskun Megyei Korhaz-Onkoradiologiai Kozpont ( Site 0483)

    Kecskemét, Bács-Kiskun county, 6000

  • SZTE Szent-Gyorgyi Albert Klinikai Kozpont ( Site 0482)

    Szeged, Csongrád megye, 6720

Other trials in Hungary

Israel5 sites

  • Rambam Medical Center ( Site 0524)

    Haifa, 3109601

  • Haddassah Medical Organization - Ein Kerem ( Site 0519)

    Jerusalem, 9112001

  • Rabin Medical Center ( Site 0520)

    Petah Tikva, 4941492

  • Chaim Sheba Medical Center ( Site 0523)

    Ramat Gan, 5262000

  • Sourasky Medical Center ( Site 0522)

    Tel Aviv, 6423906

Other trials in Israel

Belgium4 sites

  • Erasme Hospital ( Site 0376)

    Brussels, Bruxelles-Capitale, Region de, 1070

  • University Hospital Antwerp (UZA) ( Site 0374)

    Edegem, Antwerpen, 02650

  • UZ Gent ( Site 0375)

    Ghent, Oost-Vlaanderen, 9000

  • UZ Leuven ( Site 0377)

    Leuven, Vlaams-Brabant, 3000

Other trials in Belgium

Hong Kong4 sites

  • Prince of Wales Hospital ( Site 0268)

    Hong Kong, 000

  • Pamela Youde Nethersole Eastern Hospital ( Site 0271)

    Hong Kong

  • Queen Mary Hospital ( Site 0267)

    Hong Kong

  • Tuen Mun Hospital ( Site 0272)

    Tuenmen

Other trials in Hong Kong

Sweden4 sites

  • Sahlgrenska Universitetssjukhuset ( Site 0691)

    Gothenburg, Västra Götaland County, 413 46

  • Skane University Hospital ( Site 0692)

    Malmö, Skåne County, 205 02

  • Karolinska Universitetssjukhuset, Huddinge ( Site 0689)

    Stockholm, Stockholm County, 141 86

  • Norrlands Universitetssjukhus ( Site 0687)

    Umeå, Västerbotten County, 901 85

Other trials in Sweden

Thailand4 sites

  • Ramathibodi Hospital. ( Site 0352)

    Bangkok, Bangkok, 10400

  • Siriraj Hospital ( Site 0351)

    Bangkok, Bangkok, 10700

  • Maharaj Nakorn Chiangmai Hospital ( Site 0353)

    Chiang Mai, 50200

  • Srinagarind Hospital ( Site 0354)

    Khon Kaen, 40002

Other trials in Thailand

Canada3 sites

  • Nova Scotia Health Authority QEII-HSC ( Site 0208)

    Halifax, Nova Scotia, B3H 2Y9

  • Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0211)

    Montreal, Quebec, H2X 3E4

  • McGill University Health Centre ( Site 0207)

    Montreal, Quebec, H4A 3J1

Other trials in Canada

Denmark3 sites

  • Aarhus Universitets hospital ( Site 0420)

    Aarhus N, Central Jutland, 8200

  • Herlev Hospital ( Site 0421)

    Herlev, Capital Region, 2730

  • Odense Universitets Hospital ( Site 0422)

    Odense C, Region Syddanmark, 5000

Other trials in Denmark

Ireland2 sites

  • St Vincent's University Hospital ( Site 0498)

    Dublin, D04 T6F4

  • Tallaght University Hospital ( Site 0499)

    Dublin, D24 NR0A

Other trials in Ireland

New Zealand2 sites

  • Auckland City Hospital ( Site 0246)

    Auckland, 1142

  • Christchurch Hospital ( Site 0247)

    Christchurch, Canterbury, 8011

Other trials in New Zealand

Bulgaria1 site

  • Complex Cancer Center Plovdiv-First Medical Oncology Department ( Site 0982)

    Plovdiv, 4004

Other trials in Bulgaria

Norway1 site

  • Oslo Universitetssykehus HF. Ulleval ( Site 0433)

    Oslo, 0450

Other trials in Norway

About this study

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)

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).

Being tested
Pembrolizumab, Placebo
Keywords
Programmed Cell Death 1 (PD-1, PD1), Programmed Cell Death Ligand 1 (PD-L1, PDL1), Checkpoint Inhibitor, Immunotherapy, Adjuvant
Medical subject headings
Carcinoma, Hepatocellular, Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabBiological

    Also called KEYTRUDA®, MK-3475

    IV infusion of Pembrolizumab 200 mg.

  • PlaceboDrug

    IV infusion of 0.9% normal saline.

Study groups in NCT03867084
Study groupRoleWhat they receive
PembrolizumabExperimentalParticipants receive intravenous (IV) pembrolizumab at 200 mg on Day 1 of each 21-day cycle for up to 17 cycles.
Receives: Biological: Pembrolizumab
PlaceboPlacebo comparatorParticipants receive IV placebo on Day 1 of each 21-day cycle for up to 17 cycles.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Recurrence-Free Survival (RFS)

    RFS was defined as the time from randomization to first documentation of disease recurrence (local, regional, or distant) as assessed by blinded independent central review (BICR) or by pathology consistent with HCC if required per the site's standard of care, or death due to any cause (both cancer and non-cancer causes of death), whichever occurred first. RFS was reported for each arm.

    Measured: Up to approximately 69 months

  2. Overall Survival (OS)

    OS was defined as the time from randomization to death due to any cause. OS was reported for each arm.

    Measured: Up to approximately 69 months

Secondary outcomes (15)

  1. Number of Participants Who Experienced an Adverse Event (AE)

    An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy was determined. The number of participants who experienced an AE were reported.

    Measured: Up to approximately 26 months

  2. Number of Participants Who Discontinued Study Treatment Due to an AE

    An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy was determined. The number of participants who discontinued study treatment due to an AE were reported.

    Measured: Up to approximately 23 months

  3. 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

    The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participants responded to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life ("How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). The combined score of GHS (Item 29) and QoL (Item 30) was computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicated a better outcome. The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QoL (EORTC QLQ-C30 Item 30) combined score was reported.

    Measured: Baseline and up to approximately 120 weeks

  4. Change From Baseline in EORTC QLQ-C30 Physical Functioning Scale Score

    The EORTC QLQ-C30 is a cancer specific health-related quality of life questionnaire. Participants responded to 5 questions about their physical functioning (Items 1-5) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 was computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. Higher scores indicated better physical functioning. The change from baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) combined score was reported.

    Measured: Baseline and up to approximately 120 weeks

  5. Change From Baseline in EORTC QLQ-C30 Role Functioning Scale Score

    The EORTC QLQ-C30 is a cancer specific health-related quality of life questionnaire. The role functioning score was based on participant responses to questions scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score was computed by averaging the raw scores of Items 6 and 7 and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. Higher scores indicated better role functioning. The change from baseline in EORTC QLQ-C30 Role Functioning (Items 6 and 7) combined score was reported.

    Measured: Baseline and up to approximately 120 weeks

  6. Change From Baseline in EORTC QLQ-Hepatocellular Carcinoma Module (EORTC QLQ-HCC18) Abdominal Swelling Scale Score

    The EORTC QLQ-HCC18 is an HCC-specific questionnaire, administered in addition to the EORTC QLQ-C30. The abdominal swelling scale score was based on participant responses to questions scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores were standardized, so that scores range from 0-100. Higher scores indicated more severe symptoms/problems. Change from baseline in the EORTC QLQ-HCC18 abdominal swelling scale score was reported.

    Measured: Baseline and up to approximately 120 weeks

  7. Change From Baseline in EORTC QLQ-HCC18 Fatigue Scale Score

    The EORTC QLQ-HCC18 is an HCC-specific questionnaire, administered in addition to the EORTC QLQ-C30. The fatigue scale score was based on participant responses to questions scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score was computed by averaging the raw scores of the items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. Higher scores indicated more severe symptoms/problems. Change from baseline in the EORTC QLQ-HCC18 fatigue scale score was reported.

    Measured: Baseline and up to approximately 120 weeks

  8. Change From Baseline in EORTC QLQ-HCC18 Pain Scale Score

    The EORTC QLQ-HCC18 is an HCC-specific questionnaire, administered in addition to the EORTC QLQ-C30. The pain scale score was based on participant responses to questions scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score was computed by averaging the raw scores of the items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. Higher scores indicated more severe symptoms/problems. Change from baseline in the EORTC QLQ-HCC18 pain scale score was reported.

    Measured: Baseline and up to approximately 120 weeks

  9. Change From Baseline in Visual Analogue Scale (VAS) Score on the European Quality of Life (EuroQoL)-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Health Utility Score

    The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. The VAS is a component of the EQ-5D-5L that asked participants to rate their overall health on a vertical visual analogue scale, with the scale's ends labelled 'The best health you can imagine' (equivalent to a score of 0) and 'The worst health you can imagine' (equivalent to a score of 100).

    Measured: Baseline and up to approximately 120 weeks

  10. Time to Deterioration (TTD) in the EORTC QLQ-C30 Combined GHS / QoL Scale Score

    EORTC QLQ-C30 is a questionnaire to assess QoL of cancer patients. Participants responded to questions on GHS ("How would you rate your overall health during the past week?") and QoL ("How would you rate your overall QoL during the past week?") were scored on a 7-point scale (1= Very poor to 7=Excellent). The combined score of GHS (Item 29) and QoL (Item 30) was computed by averaging raw scores of the 2 items and applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicated a better outcome. TTD was defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in GHS-QoL combined score. A longer TTD indicated a better outcome.

    Measured: Baseline and up to approximately 120 weeks

  11. TTD in the EORTC QLQ-C30 Physical Functioning Scale Score

    EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participants responded to 5 questions about their physical functioning (Items 1 to 5) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 was computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicated a better outcome. TTD was defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in physical functioning (Items 1 to 5). A longer TTD indicated a better outcome.

    Measured: Baseline and up to approximately 120 weeks

  12. TTD in the EORTC QLQ-C30 Role Functioning Scale Score

    EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participants responded to questions about their role functioning (Items 6 and 7) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of Items 6 and 7 was computed by averaging the raw scores of the items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicated a better outcome. TTD was defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in physical functioning (Items 6 and 7). A longer TTD indicated a better outcome.

    Measured: Baseline and up to approximately 120 weeks

  13. TTD in the EORTC QLQ-HCC18 Abdominal Swelling Scale Score

    The EORTC QLQ-HCC18 is an HCC-specific questionnaire, administered in addition to the EORTC QLQ-C30. The abdominal swelling scale score was based on participant responses to questions scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores were standardized, so that scores range from 0-100. Higher scores indicated more severe symptoms/problems. The TTD in EORTC QLQ-HCC18 abdominal swelling scale score was reported, defined as the time to first onset of a ≥10 point decrease from baseline.

    Measured: Baseline and up to approximately 120 weeks

  14. TTD in the EORTC QLQ-HCC18 Fatigue Scale Score

    The EORTC QLQ-HCC18 is an HCC-specific questionnaire, administered in addition to the EORTC QLQ-C30. The fatigue scale score was based on participant responses to questions scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score was computed by averaging the raw scores of the items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. Higher scores indicated more severe symptoms/problems. The TTD in EORTC QLQ-HCC18 fatigue scale score was reported, defined as the time to first onset of a ≥10 point decrease from baseline.

    Measured: Baseline and up to approximately 120 weeks

  15. TTD in the EORTC QLQ-HCC18 Pain Scale Score

    The EORTC QLQ-HCC18 is an HCC-specific questionnaire, administered in addition to the EORTC QLQ-C30. The pain scale score was based on participant responses to questions scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score was computed by averaging the raw scores of the items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. Higher scores indicated more severe symptoms/problems. The TTD in EORTC QLQ-HCC18 pain scale score was reported, defined as the time to first onset of a ≥10 point decrease from baseline.

    Measured: Baseline and up to approximately 120 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Mar 2019
  2. Study start28 May 2019
  3. Primary completion20 Mar 2025
  4. Study completion30 Sep 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
959 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03867084
Sponsor's protocol ID
3475-937
Other IDs
MK-3475-937, KEYNOTE-937, 194786, 2022-501971-24-00, U1111-1282-6370, 2018-004800-20, 2018
Status last verified
Apr 2026
First submitted
6 Mar 2019
Last updated
24 Apr 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

  • Verset G, Borbath I, Karwal M, Verslype C, Van Vlierberghe H, Kardosh A, Zagonel V, Stal P, Sarker D, Palmer DH, Vogel A, Edeline J, Cattan S, Kudo M, Cheng AL, Ogasawara S, Daniele B, Chan SL, Knox JJ, Qin S, Siegel AB, Chisamore M, Hatogai K, Wang A, Finn RS, Zhu AX. Pembrolizumab Monotherapy for Previously Untreated Advanced Hepatocellular Carcinoma: Data from the Open-Label, Phase II KEYNOTE-224 Trial. Clin Cancer Res. 2022 Jun 13;28(12):2547-2554. doi: 10.1158/1078-0432.CCR-21-3807.

    PubMed 35421228

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pembrolizumab in people with Hepatocellular Carcinoma, run by Merck Sharp & Dohme LLC at 249 sites in 31 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 249 sites in United States, Japan, China, Russia, Germany and 26 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Apr 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recurrence-Free Survival (RFS) (time frame: Up to approximately 69 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03867084, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2026; AzTrials last refreshed its copy on 8 Nov 2026.

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