NCT03062358 · CITED IN SOURCE DOCUMENTS

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)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2025-09-30

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Number of Participants Who Discontinued Study Treatment Due to an AE

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * 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. * 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 Exclusion Criteria: * 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 * 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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Participants receive pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.
intervention Names
Biological: pembrolizumab
Other: best supportive care (BSC)
label
pembrolizumab + BSC
type
EXPERIMENTAL
description
Participants receive placebo by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.
intervention Names
Drug: placebo
Other: best supportive care (BSC)
label
placebo + BSC
type
PLACEBO_COMPARATOR

interventions

arm Group Labels
pembrolizumab + BSC
description
Administered as an intravenous (IV) infusion every 3 weeks (Q3W)
name
pembrolizumab
other Names
KEYTRUDA®
type
BIOLOGICAL
arm Group Labels
placebo + BSC
description
Normal saline solution administered as an IV infusion Q3W
name
placebo
type
DRUG
arm Group Labels
pembrolizumab + BSC
placebo + BSC
description
BSC will include pain management and management of other potential complications including ascites per local standards of care.
name
best supportive care (BSC)
type
OTHER

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: DOUBLE
who Masked: PARTICIPANT
INVESTIGATOR

primary Purpose

TREATMENT

Enrollment

count: 453
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
OS is the time from randomization to death due to any cause, based on the Kaplan-Meier method for censored data.
measure
Overall Survival (OS)
time Frame
Up to approximately 4 years

secondary Outcomes

description
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.
measure
Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
time Frame
Up to approximately 4 years
description
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.
measure
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
time Frame
Up to approximately 4 years
description
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.
measure
Duration Of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
time Frame
Up to approximately 4 years
description
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.
measure
Disease Control Rate (DCR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
time Frame
Up to approximately 4 years
description
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.
measure
Time To Progression (TTP) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
time Frame
Up to approximately 4 years
description
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.
measure
Number of Participants Who Experienced At Least One Adverse Event (AE)
time Frame
Up to approximately 30 months.
description
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.
measure
Number of Participants Who Discontinued Study Treatment Due to an AE
time Frame
Up to approximately 27 months.

Full study description

brief 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). The primary hypothesis of this study is that overall survival is prolonged in participants who receive pembrolizumab compared to those who receive placebo.

Source references

references

citation
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.
pmid
36455168
type
BACKGROUND
citation
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.
pmid
40486134
type
DERIVED