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)

Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03062358
Collaborator
(none)
454
41
2
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11.1
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Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • Biological: pembrolizumab
  • Drug: placebo
  • Other: best supportive care (BSC)
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
454 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Apr 27, 2017
Actual Primary Completion Date :
Jun 30, 2021
Anticipated Study Completion Date :
Jun 30, 2023

Arms and Interventions

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.

    Drug: placebo
    Normal saline solution administered as an IV infusion Q3W

    Other: best supportive care (BSC)
    BSC will include pain management and management of other potential complications including ascites per local standards of care.

    Outcome Measures

    Primary Outcome Measures

    1. Overall Survival (OS) [Up to approximately 2 years]

      OS is the time from randomization to death due to any cause.

    Secondary Outcome Measures

    1. Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [Up to approximately 2 years]

      PFS is the time from randomization to first documented disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR).

    2. Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [Up to approximately 2 years]

      ORR is the proportion of the participants who achieve complete response (CR) or partial response (PR) per RECIST 1.1 by Blinded Independent Central Review (BICR).

    3. Duration Of Response (DOR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [Up to approximately 2 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 Blinded Independent Central Review (BICR) or death.

    4. Disease Control Rate (DCR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [Up to approximately 2 years]

      DCR is the percentage of participants who achieve CR, PR, or stable disease (SD) for ≥6 weeks prior to evidence of disease progression per RECIST 1.1 by Blinded Independent Central Review (BICR).

    5. Time To Progression (TTP) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [Up to approximately 2 years]

      TTP is the time from randomization to first documented disease progression per RECIST 1.1 by Blinded Independent Central Review (BICR).

    6. Number of Participants Who Experienced At Least One Adverse Event (AE) [From time of signing the informed consent form (ICF) until the end of follow-up (up to approximately 118 weeks)]

      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.

    7. Number of Participants Who Discontinued Study Treatment Due to an AE [From time of signing the ICF until the end of study medication (up to approximately 105 weeks)]

      The number of participants discontinuing study drug due to an AE will be presented.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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) or other site 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

    Contacts and Locations

    Locations

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

    Sponsors and Collaborators

    • Merck Sharp & Dohme LLC

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT03062358
    Other Study ID Numbers:
    • 3475-394
    • MK-3475-394
    First Posted:
    Feb 23, 2017
    Last Update Posted:
    Mar 4, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Merck Sharp & Dohme LLC
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Mar 4, 2022