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)
- Conditions
- Carcinoma, Hepatocellular
- Interventions
- Registration Number
- NCT03062358
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 453
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description pembrolizumab + BSC best supportive care (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. placebo + BSC best supportive care (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. placebo + BSC placebo Participants receive placebo by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC. pembrolizumab + BSC pembrolizumab Participants receive pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) 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.
- Secondary Outcome Measures
Name Time Method Disease Control Rate (DCR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) 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.
Number of Participants Who Experienced At Least One Adverse Event (AE) 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.
Number of Participants Who Discontinued Study Treatment Due to an AE 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.
Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) 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.
Duration Of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) 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.
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) 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.
Time To Progression (TTP) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) 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.
Trial Locations
- Locations (41)
Beijing Cancer Hospital ( Site 0010)
🇨🇳Beijing, China
Zhongshan Hospital Fudan University ( Site 0012)
🇨🇳Shanghai, China
Renji Hosp,Shanghai Jiao Tong University School of Medicine ( Site 0017)
🇨🇳Shanghai, China
Hospital Universiti Kebangsaan Malaysia ( Site 0093)
🇲🇾Cheras, Malaysia
China Medical University Hospital ( Site 0131)
🇨🇳Taichung, Taiwan
The First Affiliated Hospital of Anhui Medical University ( Site 0005)
🇨🇳Hefei, Anhui, China
Anhui Provincial Hospital ( Site 0032)
🇨🇳Hefei, Anhui, China
Guangdong General Hospital ( Site 0015)
🇨🇳Guangzhou, Guangdong, China
Harbin Medical University Cancer Hospital ( Site 0007)
🇨🇳Harbin, Heilongjiang, China
Wuhan Tongji Hospital ( Site 0021)
🇨🇳Wuhan, Hubei, China
Fuzhou General Hospital of Nanjing Military Command ( Site 0019)
🇨🇳Fuzhou, Fujian, China
The First People s Hospital of Foshan ( Site 0033)
🇨🇳Foshan, Guangdong, China
Hunan Cancer Hospital ( Site 0027)
🇨🇳Changsha, Hunan, China
The Third Xiangya Hospital of Central South University ( Site 0026)
🇨🇳Changsha, Hunan, China
Nantong Tumor Hospital ( Site 0028)
🇨🇳Nantong, Jiangsu, China
Hubei Cancer Hospital ( Site 0035)
🇨🇳Wuhan, Hubei, China
The First Affiliated Hospital of Soochow University ( Site 0025)
🇨🇳Suzhou, Jiangsu, China
Jiangsu Cancer Hospital ( Site 0003)
🇨🇳Nanjing, Jiangsu, China
The 81st Hospital of PLA ( Site 0016)
🇨🇳Nanjing, Jiangsu, China
Yangzhou No.1 People's Hospital ( Site 0023)
🇨🇳Yangzhou, Jiangsu, China
Zhejiang Cancer Hospital ( Site 0011)
🇨🇳Hangzhou, Zhejiang, China
The First Hospital Of Jilin University ( Site 0001)
🇨🇳Chang Chun, Jilin, China
The First Affiliated Hospital of Dalian Medical University ( Site 0022)
🇨🇳Dalian, Liaoning, China
West China Hospital of Sichuan University ( Site 0030)
🇨🇳Chengdu, Sichuan, China
Jilin Province Cancer Hospital, Department of Chemotherapy ( Site 0002)
🇨🇳Changchun, Jilin, China
The first affiliated Hospital of Xi an Jiaotong University ( Site 0014)
🇨🇳XI An, Shanxi, China
Fudan University Shanghai Cancer Center ( Site 0024)
🇨🇳Shanghai, Shanghai, China
The First affiliated Hospital Zhejing University ( Site 0034)
🇨🇳Hangzhou, Zhejiang, China
Bengbu Medical College First Affiliated Hospital ( Site 0020)
🇨🇳Bengbu, China
The Second Affiliated Hospital of Anhui Medical University ( Site 0008)
🇨🇳Hefei, China
Princess Margaret Hospital. ( Site 0051)
🇭🇰Hong Kong, Hong Kong
Asan Medical Center ( Site 0072)
🇰🇷Seoul., Korea, Republic of
Beacon Hospital Sdn Bhd ( Site 0092)
🇲🇾Petaling Jaya, Selangor, Malaysia
Chia-Yi Chang Gung Memorial Hospital ( Site 0133)
🇨🇳Chiayi, Taiwan
University Malaya Medical Centre ( Site 0091)
🇲🇾Kuala Lumpur, Wilayah Persekutuan, Malaysia
National Cheng Kung University Hospital ( Site 0132)
🇨🇳Tainan, Taiwan
Seoul National University Hospital ( Site 0074)
🇰🇷Seoul, Korea, Republic of
Severance Hospital Yonsei University Health System ( Site 0073)
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center ( Site 0071)
🇰🇷Seoul, Korea, Republic of
Hong Kong Sanatorium Hospital ( Site 0053)
🇭🇰Hong Kong, Hong Kong
Pamela Youde Nethersole Eastern Hospital ( Site 0052)
🇭🇰Hong Kong, Hong Kong