Phase 3 Study of Tislelizumab Versus Sorafenib in Participants With Unresectable HCC
- Conditions
- Hepatocellular Carcinoma (HCC)
- Interventions
- Registration Number
- NCT03412773
- Lead Sponsor
- BeiGene
- Brief Summary
This is a Phase 3, randomized, open-label, multicenter, global study designed to compare the efficacy and safety of tislelizumab versus sorafenib as a first-line systemic treatment in participants with unresectable hepatocellular carcinoma. This study also includes a substudy investigating the safety, tolerability, PK, and preliminary efficacy in HCC in Japanese participants. In Japan, preliminary safety and tolerability will be evaluated (Safety Run-In Substudy) before Japanese participants are recruited in this Phase 3 study.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 674
- Histologically confirmed diagnosis of HCC
- Barcelona Clinic Liver Cancer (BCLC) Stage B or C disease not amenable to or progressing after loco-regional therapy and not amenable to a curative treatment approach
- No prior systemic therapy for HCC (with the exception of HCC participants enrolled in the safety run-in substudy [Japan only])
- Measurable disease
- Child-Pugh score A
- Easter Cooperative Oncology Group (ECOG) Performance Status ≤ 1
- Adequate organ function
Key
- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC histology
- Tumor thrombus involving main trunk of portal vein or inferior vena cava
- Loco-regional therapy to the liver within 28 days before randomization
- Clinical evidence of portal hypertension with bleeding esophageal or gastric varices at Screening, or within 6 months before randomization
- Bleeding or thrombotic disorder or any prescribed anticoagulant requiring therapeutic international normalized ratio monitoring (eg, warfarin or similar agents) at Screening, or within 6 months before randomization/enrollment
- Presence at Screening of active immune deficiency or autoimmune disease and/or prior history of any immune deficiency or autoimmune disease that may relapse
- Participant with any condition requiring systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication within 14 days before randomization
- History of interstitial lung disease or non-infectious pneumonitis, unless induced by radiation therapy
- QT interval corrected for heart rate (QTc) (corrected by Fridericia's method) > 450 msec at Screening
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Tislelizumab & Safety Run-In Substudy [Japan Only] Tislelizumab - Arm B: Sorafenib Sorafenib -
- Primary Outcome Measures
Name Time Method Safety Run-In Substudy[Japan only]: Percentage of Participants With Clinically Significant Changes in Physical Examination Findings From date of enrollment up to 4 years, approximately. Overall Survival (OS) From date of randomization up to 4 years, approximately Safety Run-In Substudy[Japan only]: Percentage of participants with adverse events From date of enrollment up to 4 years, approximately. Safety Run-In Substudy[Japan only]: Percentage of participants with dose-limiting toxicities (DLT) [Determination of the pivotal Phase 3 dose of tislelizumab in Japanese participants] From the date of enrollment up to 28 days [DLT period]. Safety Run-In Substudy[Japan only]: Maximum Concentration (Cmax) of Tislelizumab From first dose of study treatment up to 4 years, approximately. Safety Run-In Substudy[Japan only]: Percentage of Participants With Clinically Significant Changes in Clinical Laboratory Results Findings From date of enrollment up to 4 years, approximately. Safety Run-In Substudy[Japan only]: Percentage of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings From date of enrollment up to 4 years, approximately. Safety Run-In Substudy[Japan only]: Trough Serum Concentration (Cmin) of tislelizumab From first dose of study treatment up to 4 years, approximately. Safety Run-In Substudy[Japan only]: Area Under the Curve (AUC) of tislelizumab From first dose of study treatment up to 4 years, approximately. Safety Run-In Substudy[Japan only]: Percentage of Participants With Clinically Significant Changes in Vital Signs Findings From date of enrollment up to 4 years, approximately. Safety Run-In Substudy[Japan only]:Anti-Drug Antibodies (ADA) against tislelizumab at Cmin From first dose of study treatment up to 4 years, approximately.
- Secondary Outcome Measures
Name Time Method Disease Control Rate (DCR) From first dose of study treatment up to 4 years, approximately Clinical Benefit Rate (CBR) From first dose of study treatment up to 4 years, approximately Percentage of participants with adverse events From date of screening up to 4 years, approximately. Safety Run-In Substudy[Japan only]: Objective Response Rate (ORR) From date of randomization up to 4 years, approximately. Safety Run-In Substudy[Japan only]: Duration of Response (DOR) From date of randomization up 4 years, approximately Percentage of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings From date of enrollment up to 4 years, approximately Objective Response Rate (ORR) From date of randomization up to 4 years, approximately Progression-free survival (PFS) From date of randomization up to 4 years, approximately Duration of Response (DOR) From first determination of an objective response up to 4 years, approximately Time to Progression (TTP) From date of randomization up to 4 years, approximately. Health-Related Quality of Life (HRQoL) From date of enrollment up to 4 years, approximately. Safety Run-In Substudy[Japan only]: Overall Survival (OS) From date of randomization up 4 years, approximately Safety Run-In Substudy[Japan only]: Anti-tislelizumab antibody From first dose of study treatment up 4 years, approximately Percentage of Participants With Clinically Significant Changes in Vital Signs Findings From date of enrollment up to 4 years, approximately Percentage of Participants With Clinically Significant Changes in Physical Examination Findings From date of enrollment up to 4 years, approximately Percentage of Participants With Clinically Significant Changes in Clinical Laboratory Results Findings From date of enrollment up to 4 years, approximately Safety Run-In Substudy[Japan only]: Progression-free survival (PFS) From date of randomization up 4 years, approximately
Trial Locations
- Locations (143)
University of California - Hematology and Oncology
🇺🇸Los Angeles, California, United States
Cancer Treatment Centers of America - Oncology
🇺🇸Philadelphia, Pennsylvania, United States
UMass Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
Hahnemann University Hospital - Gastroenterology Hepatology
🇺🇸Philadelphia, Pennsylvania, United States
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
China Medical University Hospital - Transplantology - Taichung
🇨🇳Taichung, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Anhui Provincial Hospital
🇨🇳Hefei, Anhui, China
The First Affiliated Hospital Of Anhui Medical University
🇨🇳Hefei, Anhui, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, Heilongjiang, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
The First Hospital of Jilin University
🇨🇳Changchun, Jilin, China
Shanghai Cancer Hospital of Fudan University
🇨🇳Shanghai, Shanghai, China
Zhongshan Hospital Fudan University
🇨🇳Shanghai, Shanghai, China
The First Affiliated Hospital of Zhejiang University
🇨🇳HangZhou, Zhejiang, China
The First Affiliated Hospital of Chongqing Medical University
🇨🇳Chongqing, China
Tianjin Medical University Cancer Institute and Hospital
🇨🇳Tianjin, China
The First Affiliated Hospital Of XI'AN Jiaotong University
🇨🇳Xian, Shanxi, China
Southern California Research Center
🇺🇸Coronado, California, United States
University Medical Center New Orleans
🇺🇸New Orleans, Louisiana, United States
Umdnj-Njms
🇺🇸Newark, New Jersey, United States
St. Jude Heritage Healthcare
🇺🇸Fullerton, California, United States
Inland Empire Liver Foundation
🇺🇸Rialto, California, United States
Precision Cancer Research / Dayton Physicians Network
🇺🇸Kettering, Ohio, United States
Vanderbilt University Medical Center (VUMC)
🇺🇸Nashville, Tennessee, United States
Chao Family Comprehensive Cancer Center
🇺🇸Orange, California, United States
Ochsner Medical Center (OMC) - New Orleans ACCRU Network Sit
🇺🇸New Orleans, Louisiana, United States
Healthcare Research Network III, LLC
🇺🇸Tinley Park, Illinois, United States
Northwell Health/Monter Cancer Center
🇺🇸Lake Success, New York, United States
The First Affiliated Hospital of Bengbu Medical College
🇨🇳Bengbu, Anhui, China
Anhui Medical University - The Second Hospital
🇨🇳Hefei, Anhui, China
Nanfang Hospital
🇨🇳Guangzhou, Guangdong, China
Chinese PLA General Hospital
🇨🇳Beijing, Beijing, China
The Mays Cancer Center
🇺🇸San Antonio, Texas, United States
Jiangsu Cancer Hospital
🇨🇳Nanjing, Jiangsu, China
302 Military Hospital of China
🇨🇳Beijing, Beijing, China
Cancer Hopital Chinese Academy of Medical Sciences
🇨🇳Beijing, Beijing, China
CHU Nantes -hopital hotel Dieu
🇫🇷Nantes, Loire-Atlantique, France
Maria Gonzalez-Carmona
🇩🇪Bonn, Nordrhein-Westfalen, Germany
Hubei Cancer Hospital
🇨🇳Wuhan, Hubei, China
Fujian Medical University Union Hospital
🇨🇳Fuzhou, Fujian, China
Jilin Cancer Hospital
🇨🇳Changchun, Jilin, China
Weifang People's Hospital
🇨🇳Weifang, Shandong, China
CHU de Grenoble Alpes
🇫🇷La Tronche, Isere, France
The First Affiliated Hospital of Soochow University
🇨🇳Suzhou, Jiangsu, China
The Second Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
Zhongnan Hospital of Wuhan University
🇨🇳Wuhan, Wuhan, China
Kyushu Medical Center
🇯🇵Fukuoka, Japan
Kanagawa Cancer Center
🇯🇵Yokohama, Kanagawa, Japan
CHU Saint Etienne
🇫🇷Rahon, Lyon, France
Kumamoto University Hospital
🇯🇵Kumamoto, Japan
Hyogo College of Medicine Hospital
🇯🇵Nishinomiya-shi, Japan
CHU de Nice - Hôpital de l'Archet II
🇫🇷Nice, Provence-Alpes-Côte-d'Azur, France
CHRU De Lille - Hôpital Claude Huriez
🇫🇷Lille, Nord, France
Hopital Paul Brousse- Aphp Hopitaux Universitairees Paris Su
🇫🇷Villejuif, Lie-de-France, France
Sir Run Run Shaw Hospital, Zhejiang University
🇨🇳Hangzhou, Zhejiang, China
Hospital of Poitiers
🇫🇷Poitiers, Vienne, France
CHU Cote De Nacre - Hepato-Gastro-Enterologie Et N
🇫🇷Caen, Cedex 05, Basse-Normandie, France
Stefan Pluntke
🇩🇪Essen, Nordrhein-Westfalen, Germany
Hopital Robert DEBRE, CHU Reims
🇫🇷Reims, Champagne-Ardenne, France
CHU Saint Eloi - Pôle Digestif
🇫🇷Bretagne, Rennes Cedex, France
Universitätsklinikum Leipzig AöR
🇩🇪Leipzig, Germany
Policlinico S.Orsola Malpighi, AOU di Bologna - SSD Malattie
🇮🇹Bologna, Italy
Ospedale S.Bortolo, AULSS n.6 Vicenza
🇮🇹Vicenza, Veneto, Italy
Universitätsklinikum Düsseldorf
🇩🇪Düsseldorf, Germany
Nagasaki Medical Center
🇯🇵Omura, Nagasaki, Japan
University Hospital, Kyoto Prefectural Univ of Medicine
🇯🇵Kyoto-shi, Kyôto [Kyoto], Japan
Wakayama Medical University
🇯🇵Wakayama-shi, Japan
Chi Mei Medical Center - YongKang
🇨🇳Tainan, Taiwan
King's College Hospital NHS Foundation Trust
🇬🇧London, United Kingdom
The Christie NHS Foundation Trust - Oak Road Treatment Centre
🇬🇧Withington, United Kingdom
Ist. Clinici Scientifici Maugeri - Unità Operativa di Oncologia
🇮🇹Pavia, Italy
Queen Elizabeth Hospital - Clinical Reasearch
🇬🇧Birmingham, United Kingdom
Royal Free Hospital London NHS Trust
🇬🇧London, United Kingdom
Ehime Prefectural Central Hospital - Gastroenterology
🇯🇵Matsuyama, Ehime, Japan
Osaka University Hospital
🇯🇵Suita, Osaka, Japan
Iwate Medical University Hospital
🇯🇵Morioka, Japan
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Universitätsklinikum Köln
🇩🇪Köln, Germany
Universitätsmedizin Mainz
🇩🇪Mainz, Germany
Wuhan Union Hospital
🇨🇳Wuhan, Hubei, China
Nanjing Bayi Hospital
🇨🇳Nanjing, Jiangsu, China
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
Ingalls Memorial Hospital
🇺🇸Harvey, Illinois, United States
White Plains Hospital Center for Cancer Care - Oncology
🇺🇸White Plains, New York, United States
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
Beijing YouAn Hospital, Capital Medical University
🇨🇳Beijing, Beijing, China
Fujian Provincial Cancer Hospital
🇨🇳Fuzhou, Fujian, China
Sun Yat-sen Memorial Hospital , Sun Yat-sen University
🇨🇳Guangzhou, Guangdong, China
Guangdong General Hospital
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospital of Guangxi Medical University
🇨🇳Nanning, Guangxi, China
The First Affiliated Hospital, Sun Yat-sen University
🇨🇳Guangzhou, Guangdong, China
Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital
🇨🇳Sichuan, Sichuan, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China
The Affiliated Hospital Of Qingdao University
🇨🇳Qingdao, Shandong, China
Peking Union Medical College Hospital
🇨🇳Beijing, China
Fakultni nemocnice Brno
🇨🇿Brno, Brno-Mesto, Czechia
CHU Amiens-Hopital Nord - Hépato-Gastroentérologie
🇫🇷Somme, Amiens, France
Fakultni nemocnice v Motole
🇨🇿Praha 5, Czechia
Fakultni nemocnice Olomouc
🇨🇿Olomouc, Czechia
Hôpital Privé des Côtes d'Armor - Service oncologie
🇫🇷Plérin, Bretagne, France
Hospitalier Jean Minjoz
🇫🇷Besançon, Franche-Comté, France
Bichat-Beaujon Service Inter Hospitalier De Cancerologie
🇫🇷Clichy Cedex, Lie-de-France, France
Krankenhaus Nordwest gGmbH
🇩🇪Frankfurt/Main, Hessen, Germany
IRCCS Saverio De Bellis, AO Gastroenterologia
🇮🇹Castellana Grotte, Bari, Italy
PO G.Rodolico, AOU Policlinico-Vittorio Emanuele di Catania
🇮🇹Catania, Catani, Italy
PO di Cremona, ASST di Cremona - Oncologia - Cremona - Radiology
🇮🇹Cremona, Italy
Ospedale Vito Fazzi, ASL Lecce
🇮🇹Lecce, Italy
AOU Policlinico di Modena
🇮🇹Modena, Italy
IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
Regina Elena, Istituto Nazionale dei Tumori, IFO, IRCCS
🇮🇹Roma, Italy
PO Umberto I, AO Ordine Mauriziano
🇮🇹Torino, Italy
Fujita Health University Hospital
🇯🇵Toyoake, Aiti [Aichi], Japan
Ogaki Municipal Hospital
🇯🇵Ogaki, Gihu [Gifu], Japan
Hokkaido University Hospital - Gastroenterology
🇯🇵Sapporo, Hokkaidô [Hokkaido], Japan
Kanazawa University Hospital
🇯🇵Kanazawa-shi, Isikawa [Ishikawa], Japan
Yokohama City University Medical Center
🇯🇵Yokohama, Kanagawa, Japan
Kinki University Hospital, Faculty of Medicine - Hematology & Clinical Oncology
🇯🇵Osaka-sayama, Osaka, Japan
Nihon University Itabashi Hospital - Gastroenterological surgery
🇯🇵Itabashi-ku, Tôkyô [Tokyo], Japan
Chiba University Hospital
🇯🇵Chiba, Tiba [Chiba], Japan
JRC Medical Center
🇯🇵Shibuya-ku, Tôkyô [Tokyo], Japan
National Center for Global Health and Medicine
🇯🇵Shinjuku-ku, Tôkyô [Tokyo], Japan
Osaka International Cancer Institute
🇯🇵Osaka, Japan
Osaka City General Hospital
🇯🇵Osaka, Ôsaka [Osaka], Japan
Tottori University Hospital
🇯🇵Tottori, Japan
Osaka National Hospital
🇯🇵Osaka, Ôsaka [Osaka], Japan
Osaka City University Hospital
🇯🇵Osaka, Ôsaka [Osaka], Japan
Institut Catalá d´Oncología (I.C.O.)
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
Hospital Universitario Madrid Sanchinarro Centro integral Oncologico Clara Campal (CIOCC)
🇪🇸Madrid, Spain
Hospital Universitario Vall d'Hebrón
🇪🇸Barcelona, Spain
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
Chang Gung Medical Foundation - LinKou Chang Gung Memorial Hospital
🇨🇳Taipei, Taiwan
Kaohsiung Medical University - Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Tri-Service General Hospital - Neihu Branch
🇨🇳New Taipei, Taiwan
Sasaki Foundation Kyoundo Hospital
🇯🇵Chiyoda-Ku, Tokyo, Japan
Gustave Roussy - Medical Oncology
🇫🇷Villejuif, Val-de-Marne, France
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdańsk, Poland
Medical Oncology
🇮🇹Feltre, Belluno, Italy
Clinical Research Center Sp. z o.o., Medic-R Sp. K.
🇵🇱Poznan, Wielkopolskie, Poland
Wojewodzki Szpital Specjalistyczny im. Gromkowskiego we Wroclawiu
🇵🇱Wroclaw, Poland
Chang Gung Medical Foundation - Kaohsiung Chang Gung Memorial Hospital - Gastroenterology
🇨🇳Kaohsiung, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Centrum Onkologii Instytut im. M. Sklodowskiej-Curie
🇵🇱Warszawa, Mazowieckie, Poland