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Carcinoma, HepatocellularPhase 3NCT03062358

Study of Pembrolizumab (MK-3475) or Placebo Given With Best Supportive Care in Asian Participants With Previously Treated Advanced Hepatocellular Carcinoma (MK-3475-394/KEYNOTE-394)

A Phase 3 study testing pembrolizumab in people with Carcinoma, Hepatocellular, run by Merck Sharp & Dohme LLC at 41 sites in 5 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

The purpose of this study is to determine the efficacy and safety of pembrolizumab or placebo given with best supportive care (BSC) in Asian participants with previously systemically treated advanced hepatocellular carcinoma (HCC). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Hepatocellular
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
453 participants
Where
41 sitesin 5 countries
Study dates
27 Apr 2017to 15 Oct 2024
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 HCC diagnosis confirmed by radiology, histology, or cytology (fibrolamellar, and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible)
  • Has Barcelona Clinic Liver Cancer (BCLC) Stage C disease or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy and not amenable to a curative treatment approach.
  • Has a Child-Pugh A liver score within 7 days prior to first dose of study medication
  • Has a life expectancy of >3 months
  • Has at least one measurable lesion based on RECIST version 1.1 as determined by investigator.
  • Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 7 days prior to receiving the first dose of study medication.
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  • Has documented objective radiographic progression during or after treatment with sorafenib or oxaliplatin-based chemotherapy, or else intolerance to sorafenib or oxaliplatin-based chemotherapy
  • Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study therapy
  • Female and male participants of reproductive potential must agree to use adequate contraception starting from the first dose of study medication, throughout the study period, and for up to 120 days after the last dose of study medication

Who cannot join

  • Is currently participating or has participated in a study with an investigational agent or using an investigational device within 4 weeks of the first dose of study medication
  • Has received sorafenib or oxaliplatin-based chemotherapy within 14 days of first dose of study medication
  • Has had esophageal or gastric variceal bleeding within the last 6 months
  • Has clinically apparent ascites on physical examination
  • Has portal vein invasion at the main portal branch (Vp4), inferior vena cava, or cardiac involvement of HCC based on imaging
  • Has had clinically diagnosed hepatic encephalopathy in the last 6 months
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  • Has had a solid organ or hematologic transplant
  • Has had prior systemic therapy for HCC in the advanced (incurable) setting other than sorafenib or oxaliplatin-based chemotherapy, prior to start of study medication
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication
  • Has received locoregional therapy to liver (transcatheter chemoembolization [TACE], transcatheter embolization [TAE], hepatic arterial infusion [HAI], radiation, radioembolization, or ablation) within 4 weeks prior to the first dose of study medication
  • Has had major surgery to liver or other site within 4 weeks prior to the first dose of study medication
  • Has had a minor surgery ≤7 days prior to the first dose of study medication
  • Has not recovered adequately (i.e., Grade ≤1 or baseline) from the toxicity and/or complications from any intervention prior to study start
  • Has a diagnosed additional malignancy within 3 years prior to first dose of study medication with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ cancers
  • Has a known history of, or any evidence of, central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • Has an active infection requiring systemic therapy
  • Is pregnant or breast feeding or expecting to conceive or father starting from the first dose of study medication, throughout the study period, and for up to 120 days after the last dose of study medication
  • Has received prior immunotherapy with an anti-Programmed Cell Death Receptor 1 (PD-1), Programmed Cell Death Receptor Ligand 1 (anti-PD-L1), or anti-Programmed Cell Death Receptor Ligand 2 (PD-L2) or has previously participated in clinical studies with pembrolizumab
  • Has a known history of human immunodeficiency virus (HIV)
  • Has untreated active Hepatitis B
  • Has Hepatitis C in which participants received therapy for HCV <4 weeks prior to receiving pembrolizumab
  • Has received a live vaccine within 30 days prior to the first dose of study therapy

Trial locations and contacts

41 sites in 5 countries.

41 sites in 5 countries

China28 sites

  • Beijing Cancer Hospital ( Site 0010)

    Beijing, 100142

  • Bengbu Medical College First Affiliated Hospital ( Site 0020)

    Bengbu, 233030

  • Jilin Province Cancer Hospital, Department of Chemotherapy ( Site 0002)

    Changchun, Jilin, 130012

  • The First Hospital Of Jilin University ( Site 0001)

    Changchun, Jilin, 130021

  • Hunan Cancer Hospital ( Site 0027)

    Changsha, Hunan, 410006

  • The Third Xiangya Hospital of Central South University ( Site 0026)

    Changsha, Hunan, 410013

  • West China Hospital of Sichuan University ( Site 0030)

    Chengdu, Sichuan, 610000

  • The First Affiliated Hospital of Dalian Medical University ( Site 0022)

    Dalian, Liaoning, 116011

  • The First People s Hospital of Foshan ( Site 0033)

    Foshan, Guangdong, 528000

  • Fuzhou General Hospital of Nanjing Military Command ( Site 0019)

    Fuzhou, Fujian, 350025

  • Guangdong General Hospital ( Site 0015)

    Guangzhou, Guangdong, 510080

  • The First affiliated Hospital Zhejing University ( Site 0034)

    Hangzhou, Zhejiang, 310003

  • Zhejiang Cancer Hospital ( Site 0011)

    Hangzhou, Zhejiang, 310022

  • Harbin Medical University Cancer Hospital ( Site 0007)

    Harbin, Heilongjiang, 610000

  • Anhui Provincial Hospital ( Site 0032)

    Hefei, Anhui, 230001

  • The First Affiliated Hospital of Anhui Medical University ( Site 0005)

    Hefei, Anhui, 230022

  • The Second Affiliated Hospital of Anhui Medical University ( Site 0008)

    Hefei, 230601

  • Jiangsu Cancer Hospital ( Site 0003)

    Nanjing, Jiangsu, 210009

  • The 81st Hospital of PLA ( Site 0016)

    Nanjing, Jiangsu, 210031

  • Nantong Tumor Hospital ( Site 0028)

    Nantong, Jiangsu, 226361

  • Fudan University Shanghai Cancer Center ( Site 0024)

    Shanghai, Shanghai Municipality, 200032

  • Zhongshan Hospital Fudan University ( Site 0012)

    Shanghai, 200032

  • Renji Hosp,Shanghai Jiao Tong University School of Medicine ( Site 0017)

    Shanghai, 200127

  • The First Affiliated Hospital of Soochow University ( Site 0025)

    Suzhou, Jiangsu, 215006

  • Wuhan Tongji Hospital ( Site 0021)

    Wuhan, Hubei, 430030

  • Hubei Cancer Hospital ( Site 0035)

    Wuhan, Hubei, 430079

  • The first affiliated Hospital of Xi an Jiaotong University ( Site 0014)

    Xi’an, Shanxi, 710061

  • Yangzhou No.1 People's Hospital ( Site 0023)

    Yangzhou, Jiangsu, 225012

Other trials in China

South Korea4 sites

  • Seoul National University Hospital ( Site 0074)

    Seoul, 03080

  • Severance Hospital Yonsei University Health System ( Site 0073)

    Seoul, 03722

  • Asan Medical Center ( Site 0072)

    Seoul, 05505

  • Samsung Medical Center ( Site 0071)

    Seoul, 06351

Other trials in South Korea

Hong Kong3 sites

  • Hong Kong Sanatorium Hospital ( Site 0053)

    Hong Kong

  • Pamela Youde Nethersole Eastern Hospital ( Site 0052)

    Hong Kong

  • Princess Margaret Hospital. ( Site 0051)

    Hong Kong

Other trials in Hong Kong

Malaysia3 sites

  • Hospital Universiti Kebangsaan Malaysia ( Site 0093)

    Cheras, 56000

  • University Malaya Medical Centre ( Site 0091)

    Kuala Lumpur, Kuala Lumpur, 59100

  • Beacon Hospital Sdn Bhd ( Site 0092)

    Petaling Jaya, Selangor, 46050

Other trials in Malaysia

Taiwan3 sites

  • Chia-Yi Chang Gung Memorial Hospital ( Site 0133)

    Chiayi City, 613

  • China Medical University Hospital ( Site 0131)

    Taichung, 40447

  • National Cheng Kung University Hospital ( Site 0132)

    Tainan, 70403

Other trials in Taiwan

About this study

Official title: A Phase III Randomized Double-blind Study of Pembrolizumab Plus Best Supportive Care vs. Placebo Plus Best Supportive Care as Second-Line Therapy in Asian Subjects With Previously Systemically Treated Advanced Hepatocellular Carcinoma (KEYNOTE-394)

The purpose of this study is to determine the efficacy and safety of pembrolizumab or placebo given with best supportive care (BSC) in Asian participants with previously systemically treated advanced hepatocellular carcinoma (HCC). The primary hypothesis of this study is that overall survival is prolonged in participants who receive pembrolizumab compared to those who receive placebo.

Being tested
pembrolizumab, placebo, best supportive care (BSC)
Keywords
Programmed Cell Death Receptor 1 (PD-1), Programmed Cell Death Receptor Ligand 1 (PD-L1), Programmed Cell Death Receptor Ligand 2 (PD-L2), PD1, PD-1, PDL1, PD-L1, PDL2
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®

    Administered as an intravenous (IV) infusion every 3 weeks (Q3W)

  • placeboDrug

    Normal saline solution administered as an IV infusion Q3W

  • best supportive care (BSC)Other

    BSC will include pain management and management of other potential complications including ascites per local standards of care.

Study groups in NCT03062358
Study groupRoleWhat they receive
pembrolizumab + BSCExperimentalParticipants receive pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.
Receives: Biological: pembrolizumab; Other: best supportive care (BSC)
placebo + BSCPlacebo comparatorParticipants receive placebo by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.
Receives: Drug: placebo; Other: best supportive care (BSC)

What is being measured

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

  1. Overall Survival (OS)

    OS is the time from randomization to death due to any cause, based on the Kaplan-Meier method for censored data.

    Measured: Up to approximately 4 years

Secondary outcomes (7)

  1. Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

    PFS is the time from randomization to first documented disease progression or death due to any cause per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) based on the Kaplan-Meier method for censored data.

    Measured: Up to approximately 4 years

  2. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

    ORR is the percentage of participants who achieve complete response (CR) or partial response (PR) with confirmation per RECIST 1.1 by BICR. CR is the disappearance of all target lesions; PR is at least a 30% decrease in the sum of diameters of target lesions.

    Measured: Up to approximately 4 years

  3. Duration Of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

    DOR is the time from first documented evidence of CR or PR per RECIST 1.1 by BICR until disease progression per RECIST 1.1 by BICR or death, based on Kaplan-Meier method for censored data. CR is the disappearance of all target lesions; PR is at least a 30% decrease in the sum of diameters of target lesions.

    Measured: Up to approximately 4 years

  4. Disease Control Rate (DCR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

    DCR is the percentage of participants who achieve CR, PR, or stable disease (SD) for ≥5 weeks prior to evidence of disease progression per RECIST 1.1 by BICR. CR is the disappearance of all target lesions; PR is at least a 30% decrease in the sum of diameters of target lesions.

    Measured: Up to approximately 4 years

  5. Time To Progression (TTP) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

    TTP is the time from randomization to first documented disease progression per RECIST 1.1 by BICR, based on Kaplan-Meier method for censored data.

    Measured: Up to approximately 4 years

  6. Number of Participants Who Experienced At Least One Adverse Event (AE)

    An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy.

    Measured: Up to approximately 30 months.

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

    An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy.

    Measured: Up to approximately 27 months.

Timeline

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

  1. First posted23 Feb 2017
  2. Study start27 Apr 2017
  3. Primary completion30 Jun 2021
  4. Study completion15 Oct 2024

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
453 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03062358
Sponsor's protocol ID
3475-394
Other IDs
MK-3475-394
Status last verified
Sep 2025
First submitted
21 Feb 2017
Last updated
30 Sep 2025
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • Qin S, Chen Z, Fang W, Ren Z, Xu R, Ryoo BY, Meng Z, Bai Y, Chen X, Liu X, Xiao J, Ho GF, Mao Y, Wang X, Ying J, Li J, Zhong W, Zhou Y, Siegel AB, Hao C. Pembrolizumab Versus Placebo as Second-Line Therapy in Patients From Asia With Advanced Hepatocellular Carcinoma: A Randomized, Double-Blind, Phase III Trial. J Clin Oncol. 2023 Mar 1;41(7):1434-1443. doi: 10.1200/JCO.22.00620. Epub 2022 Dec 1.

    PubMed 36455168

  • Finn RS, Gu K, Chen X, Merle P, Lee KH, Bouattour M, Cao P, Wang W, Cheng AL, Zhu L, Lim HY, Kudo M, Pan Y, Chang TT, Edeline J, Li W, Yang P, Li C, Li J, Siegel AB, Qin S. Second-line pembrolizumab for advanced HCC: Meta-analysis of the phase III KEYNOTE-240 and KEYNOTE-394 studies. JHEP Rep. 2025 Feb 4;7(6):101350. doi: 10.1016/j.jhepr.2025.101350. eCollection 2025 Jun.

    PubMed 40486134

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing pembrolizumab in people with Carcinoma, Hepatocellular, run by Merck Sharp & Dohme LLC at 41 sites in 5 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 9 inclusion and 24 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 30 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 sites in China, South Korea, Hong Kong, Malaysia, Taiwan. 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 21 Mar 2023). 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?

Overall Survival (OS) (time frame: Up to approximately 4 years). 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 NCT03062358, which also lists 2 linked publications.

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 30 Sep 2025.

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