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)
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 |
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Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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:
Other: best supportive care (BSC)
BSC will include pain management and management of other potential complications including ascites per local standards of care.
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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
- Overall Survival (OS) [Up to approximately 2 years]
OS is the time from randomization to death due to any cause.
Secondary Outcome Measures
- 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).
- 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).
- 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.
- 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).
- 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).
- 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.
- 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
Inclusion Criteria:
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Has a HCC diagnosis confirmed by radiology, histology, or cytology (fibrolamellar, and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible)
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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
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Has a Child-Pugh A liver score within 7 days prior to first dose of study medication
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Has a life expectancy of >3 months
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Has at least one measurable lesion based on RECIST version 1.1 as determined by investigator
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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
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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
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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:
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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
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Has received sorafenib or oxaliplatin-based chemotherapy within 14 days of first dose of study medication
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Has had esophageal or gastric variceal bleeding within the last 6 months
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Has clinically apparent ascites on physical examination
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Has portal vein invasion at the main portal branch (Vp4), inferior vena cava, or cardiac involvement of HCC based on imaging
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Has had clinically diagnosed hepatic encephalopathy in the last 6 months
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Has had a solid organ or hematologic transplant
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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
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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.
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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
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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
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Has had major surgery to liver or other site within 4 weeks prior to the first dose of study medication
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Has had a minor surgery ≤7 days prior to the first dose of study medication
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Has not recovered adequately (i.e., Grade ≤1 or baseline) from the toxicity and/or complications from any intervention prior to study start
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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
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Has a known history of, or any evidence of, central nervous system (CNS) metastases and/or carcinomatous meningitis
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Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
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Has an active infection requiring systemic therapy
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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
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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
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Has a known history of human immunodeficiency virus (HIV)
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Has untreated active Hepatitis B
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Has Hepatitis C in which participants received therapy for HCV <4 weeks prior to receiving pembrolizumab
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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 | |
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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.- 3475-394
- MK-3475-394