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)

NCT03062358 | Completed Phase 3 Results DMC

• 2 other identifiers: 3475-394MK-3475-394
• Study Type: interventional
• Target: 453
• Locations: 5 countries
• Sites: 41

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.

Conditions

Carcinoma, Hepatocellular

Keywords

Programmed Cell Death Receptor 1 (PD-1); Programmed Cell Death Receptor Ligand 1 (PD-L1); Programmed Cell Death Receptor Ligand 2 (PD-L2); PD1; PD-1; PDL1; PD-L1; PDL2

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  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 Outcomes (7)

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

  Up to approximately 4 years

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

  Up to approximately 4 years

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

  Up to approximately 4 years

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

  Up to approximately 4 years

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

  Up to approximately 4 years

Study Arms (2)

pembrolizumab + BSC

EXPERIMENTAL

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; Other: best supportive care (BSC)

placebo + BSC

PLACEBO COMPARATOR

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; Other: best supportive care (BSC)

Interventions

pembrolizumab BIOLOGICAL

Administered as an intravenous (IV) infusion every 3 weeks (Q3W)

Also known as: KEYTRUDA®

pembrolizumab + BSC

placebo DRUG

Normal saline solution administered as an IV infusion Q3W

placebo + BSC

best supportive care (BSC) OTHER

BSC will include pain management and management of other potential complications including ascites per local standards of care.

pembrolizumab + BSC; placebo + BSC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (41)

Anhui Provincial Hospital ( Site 0032)

Hefei, Anhui, 230001, China

Location

The First Affiliated Hospital of Anhui Medical University ( Site 0005)

Hefei, Anhui, 230022, China

Location

Fuzhou General Hospital of Nanjing Military Command ( Site 0019)

Fuzhou, Fujian, 350025, China

Location

The First People s Hospital of Foshan ( Site 0033)

Foshan, Guangdong, 528000, China

Location

Guangdong General Hospital ( Site 0015)

Guangzhou, Guangdong, 510080, China

Location

Harbin Medical University Cancer Hospital ( Site 0007)

Harbin, Heilongjiang, 610000, China

Location

Wuhan Tongji Hospital ( Site 0021)

Wuhan, Hubei, 430030, China

Location

Hubei Cancer Hospital ( Site 0035)

Wuhan, Hubei, 430079, China

Location

Hunan Cancer Hospital ( Site 0027)

Changsha, Hunan, 410006, China

Location

The Third Xiangya Hospital of Central South University ( Site 0026)

Changsha, Hunan, 410013, China

Location

Jiangsu Cancer Hospital ( Site 0003)

Nanjing, Jiangsu, 210009, China

Location

The 81st Hospital of PLA ( Site 0016)

Nanjing, Jiangsu, 210031, China

Location

Nantong Tumor Hospital ( Site 0028)

Nantong, Jiangsu, 226361, China

Location

The First Affiliated Hospital of Soochow University ( Site 0025)

Suzhou, Jiangsu, 215006, China

Location

Yangzhou No.1 People's Hospital ( Site 0023)

Yangzhou, Jiangsu, 225012, China

Location

Jilin Province Cancer Hospital, Department of Chemotherapy ( Site 0002)

Changchun, Jilin, 130012, China

Location

The First Hospital Of Jilin University ( Site 0001)

Changchun, Jilin, 130021, China

Location

The First Affiliated Hospital of Dalian Medical University ( Site 0022)

Dalian, Liaoning, 116011, China

Location

Fudan University Shanghai Cancer Center ( Site 0024)

Shanghai, Shanghai Municipality, 200032, China

Location

The first affiliated Hospital of Xi an Jiaotong University ( Site 0014)

Xi’an, Shanxi, 710061, China

Location

West China Hospital of Sichuan University ( Site 0030)

Chengdu, Sichuan, 610000, China

Location

The First affiliated Hospital Zhejing University ( Site 0034)

Hangzhou, Zhejiang, 310003, China

Location

Zhejiang Cancer Hospital ( Site 0011)

Hangzhou, Zhejiang, 310022, China

Location

Beijing Cancer Hospital ( Site 0010)

Beijing, 100142, China

Location

Bengbu Medical College First Affiliated Hospital ( Site 0020)

Bengbu, 233030, China

Location

The Second Affiliated Hospital of Anhui Medical University ( Site 0008)

Hefei, 230601, China

Location

Zhongshan Hospital Fudan University ( Site 0012)

Shanghai, 200032, China

Location

Renji Hosp,Shanghai Jiao Tong University School of Medicine ( Site 0017)

Shanghai, 200127, China

Location

Hong Kong Sanatorium Hospital ( Site 0053)

Hong Kong, Hong Kong

Location

Pamela Youde Nethersole Eastern Hospital ( Site 0052)

Hong Kong, Hong Kong

Location

Princess Margaret Hospital. ( Site 0051)

Hong Kong, Hong Kong

Location

University Malaya Medical Centre ( Site 0091)

Kuala Lumpur, Kuala Lumpur, 59100, Malaysia

Location

Beacon Hospital Sdn Bhd ( Site 0092)

Petaling Jaya, Selangor, 46050, Malaysia

Location

Hospital Universiti Kebangsaan Malaysia ( Site 0093)

Cheras, 56000, Malaysia

Location

Seoul National University Hospital ( Site 0074)

Seoul, 03080, South Korea

Location

Severance Hospital Yonsei University Health System ( Site 0073)

Seoul, 03722, South Korea

Location

Asan Medical Center ( Site 0072)

Seoul, 05505, South Korea

Location

Samsung Medical Center ( Site 0071)

Seoul, 06351, South Korea

Location

Chia-Yi Chang Gung Memorial Hospital ( Site 0133)

Chiayi City, 613, Taiwan

Location

China Medical University Hospital ( Site 0131)

Taichung, 40447, Taiwan

Location

National Cheng Kung University Hospital ( Site 0132)

Tainan, 70403, Taiwan

Location

Related Publications (2)

• 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 BACKGROUND

• 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 DERIVED

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2017
• First Posted: February 23, 2017
• Study Start: April 27, 2017
• Primary Completion: June 30, 2021
• Study Completion: October 15, 2024
• Last Updated: September 30, 2025
• Results First Posted: March 21, 2023

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

TW (3); MY (3); CN (28); HK (3); KR (4)