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)

July 5, 2023 updated by: Merck Sharp & Dohme LLC

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

453

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Beijing, China, 100142
        • Beijing Cancer Hospital ( Site 0010)
      • Bengbu, China, 233030
        • Bengbu Medical College First Affiliated Hospital ( Site 0020)
      • Hefei, China, 230601
        • The Second Affiliated Hospital of Anhui Medical University ( Site 0008)
      • Shanghai, China, 200032
        • Zhongshan Hospital Fudan University ( Site 0012)
      • Shanghai, China, 200127
        • Renji Hosp,Shanghai Jiao Tong University School of Medicine ( Site 0017)
    • Anhui
      • Hefei, Anhui, China, 230001
        • Anhui Provincial Hospital ( Site 0032)
      • Hefei, Anhui, China, 230022
        • The First Affiliated Hospital of Anhui Medical University ( Site 0005)
    • Fujian
      • Fuzhou, Fujian, China, 350025
        • Fuzhou General Hospital of Nanjing Military Command ( Site 0019)
    • Guangdong
      • Foshan, Guangdong, China, 528000
        • The First People s Hospital of Foshan ( Site 0033)
      • Guangzhou, Guangdong, China, 510080
        • Guangdong General Hospital ( Site 0015)
    • Heilongjiang
      • Harbin, Heilongjiang, China, 610000
        • Harbin Medical University Cancer Hospital ( Site 0007)
    • Hubei
      • Wuhan, Hubei, China, 430030
        • Wuhan Tongji Hospital ( Site 0021)
      • Wuhan, Hubei, China, 430079
        • Hubei Cancer Hospital ( Site 0035)
    • Hunan
      • Changsha, Hunan, China, 410006
        • Hunan Cancer Hospital ( Site 0027)
      • Changsha, Hunan, China, 410013
        • The Third Xiangya Hospital of Central South University ( Site 0026)
    • Jiangsu
      • Nanjing, Jiangsu, China, 210009
        • Jiangsu Cancer Hospital ( Site 0003)
      • Nanjing, Jiangsu, China, 210031
        • The 81st Hospital of PLA ( Site 0016)
      • Nantong, Jiangsu, China, 226361
        • Nantong Tumor Hospital ( Site 0028)
      • Suzhou, Jiangsu, China, 215006
        • The First Affiliated Hospital of Soochow University ( Site 0025)
      • Yangzhou, Jiangsu, China, 225012
        • Yangzhou No.1 People's Hospital ( Site 0023)
    • Jilin
      • Chang Chun, Jilin, China, 130021
        • The First Hospital Of Jilin University ( Site 0001)
      • Changchun, Jilin, China, 130012
        • Jilin Province Cancer Hospital, Department of Chemotherapy ( Site 0002)
    • Liaoning
      • Dalian, Liaoning, China, 116011
        • The First Affiliated Hospital of Dalian Medical University ( Site 0022)
    • Shanghai
      • Shanghai, Shanghai, China, 200032
        • Fudan University Shanghai Cancer Center ( Site 0024)
    • Shanxi
      • XI An, Shanxi, China, 710061
        • The first affiliated Hospital of Xi an Jiaotong University ( Site 0014)
    • Sichuan
      • Chengdu, Sichuan, China, 610000
        • West China Hospital of Sichuan University ( Site 0030)
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310003
        • The First affiliated Hospital Zhejing University ( Site 0034)
      • Hangzhou, Zhejiang, China, 310022
        • Zhejiang Cancer Hospital ( Site 0011)
  • Hong Kong
      • Hong Kong, Hong Kong
        • Hong Kong Sanatorium Hospital ( Site 0053)
      • Hong Kong, Hong Kong
        • Pamela Youde Nethersole Eastern Hospital ( Site 0052)
      • Hong Kong, Hong Kong
        • Princess Margaret Hospital. ( Site 0051)
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03722
        • Severance Hospital Yonsei University Health System ( Site 0073)
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital ( Site 0074)
      • Seoul, Korea, Republic of, 06351
        • Samsung Medical Center ( Site 0071)
      • Seoul., Korea, Republic of, 05505
        • Asan Medical Center ( Site 0072)
  • Malaysia
      • Cheras, Malaysia, 56000
        • Hospital Universiti Kebangsaan Malaysia ( Site 0093)
    • Selangor
      • Petaling Jaya, Selangor, Malaysia, 46050
        • Beacon Hospital Sdn Bhd ( Site 0092)
    • Wilayah Persekutuan
      • Kuala Lumpur, Wilayah Persekutuan, Malaysia, 59100
        • University Malaya Medical Centre ( Site 0091)
  • Taiwan
      • Chiayi, Taiwan, 613
        • Chia-Yi Chang Gung Memorial Hospital ( Site 0133)
      • Taichung, Taiwan, 40447
        • China Medical University Hospital ( Site 0131)
      • Tainan, Taiwan, 70403
        • National Cheng Kung University Hospital ( Site 0132)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: pembrolizumab + BSC
Participants receive pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.
Biological: pembrolizumab
Administered as an intravenous (IV) infusion every 3 weeks (Q3W)
Other Names:
  • KEYTRUDA®
Other: best supportive care (BSC)
BSC will include pain management and management of other potential complications including ascites per local standards of care.
Placebo Comparator: placebo + BSC
Participants receive placebo by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.
Other: best supportive care (BSC)
BSC will include pain management and management of other potential complications including ascites per local standards of care.
Drug: placebo
Normal saline solution administered as an IV infusion Q3W

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Investigators

  • Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 27, 2017

Primary Completion (Actual)

June 30, 2021

Study Completion (Estimated)

October 31, 2024

Study Registration Dates

First Submitted

February 21, 2017

First Submitted That Met QC Criteria

February 21, 2017

First Posted (Actual)

February 23, 2017

Study Record Updates

Last Update Posted (Actual)

July 7, 2023

Last Update Submitted That Met QC Criteria

July 5, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3475-394
  • MK-3475-394 (Other Identifier: Merck Registration Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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