A Study of Tislelizumab Versus Sorafenib in Participants With Unresectable Hepatocellular Carcinoma (HCC)
A Randomized, Open-label, Multicenter Phase 3 Study to Compare the Efficacy and Safety of BGB-A317 Versus Sorafenib as First-Line Treatment in Patients With Unresectable Hepatocellular Carcinoma
5 other identifiers
interventional
684
11 countries
122
Brief Summary
This Phase 3 study was a global, multicenter trial that randomly assigned participants to either tislelizumab or sorafenib as a first-line treatment for adults with advanced liver cancer (hepatocellular carcinoma) that could not be surgically removed. Before enrolling Japanese participants in the main Phase 3 study, a preliminary assessment of safety and tolerability (the Safety Run-In Sub-study) was conducted in Japan.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Dec 2017
Longer than P75 for phase_3
122 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 18, 2017
CompletedFirst Submitted
Initial submission to the registry
January 3, 2018
CompletedFirst Posted
Study publicly available on registry
January 26, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 11, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
December 14, 2023
CompletedResults Posted
Study results publicly available
October 14, 2025
CompletedOctober 14, 2025
September 1, 2025
4.6 years
January 3, 2018
December 12, 2024
September 24, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Safety Run-in Sub-study: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) is any unfavorable or unintended sign (e.g., abnormal lab result), symptom, or disease temporally associated with study drug use, regardless of causality. A serious adverse event (SAE) is defined as any adverse event that: * Resulted in death * Was life-threatening * Required or prolonged hospitalization * Caused disability/incapacity * Lead to a congenital anomaly/birth defect * Was deemed medically significant by the investigator (e.g., required intervention to prevent severe outcomes).
From the first dose to 30 days after the last dose, new anticancer therapy, or the analysis cutoff of December 14th, 2023 (a maximum of 64 months)
Safety Run-in Sub-study: Serum Concentration of Tislelizumab
Serum concentration of tislelizumab was a pre-specified primary endpoint for the sub-study only.
Cycle 1 and Cycle 5 at end of infusion, 24 hand 72 hours post-dose, and 8 days and 15 days post-dose (each cycle was 3 weeks).
Main Study: Overall Survival (OS)
Defined as the time from the date of randomization to the date of death due to any cause. Median OS was estimated using Kaplan-Meier methodology. Overall survival was a pre-specified primary endpoint for the main study only.
Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months)
Secondary Outcomes (21)
Overall Response Rate (ORR) as Assessed by Blinded Independent Review Committee (BIRC)
Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months)
Overall Response Rate (ORR) as Assessed by the Investigator
Through the study completion data cut-off date of December 14th, 2023 (up to approximately 65 months)
Progression Free Survival (PFS) as Assessed by BIRC
Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months)
Progression Free Survival (PFS) Assessed by the Investigator
Through the study completion data cut-off date of December 14th, 2023 (up to approximately 65 months)
Duration of Response (DOR) as Assessed by BIRC
Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months)
- +16 more secondary outcomes
Study Arms (3)
Safety Run-In Sub-study
EXPERIMENTALJapanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.
Arm A: Tislelizumab
EXPERIMENTALParticipants received 200 mg of intravenous tislelizumab every 3 weeks until intolerable toxicity, withdrawal of consent, or the investigator determined no further benefit from the therapy.
Arm B: Sorafenib
ACTIVE COMPARATORParticipants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
Interventions
Tislelizumab 200 mg intravenously (IV) once every three weeks (Q3W)
Sorafenib 400 mg orally (PO) twice daily (BID)
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- BeiGenelead
Study Sites (122)
Providence Medical Foundation
Fullerton, California, 92835, United States
UCLA Hematologyoncology
Los Angeles, California, 90095, United States
Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Umdnj Njms
Newark, New Jersey, 07840, United States
Rj Zuckerberg Cancer Center
Lake Success, New York, 11042, United States
Xcancerdayton Physician Network
Dayton, Ohio, 45409, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
Ut Health San Antonio Mays Cancer Center
San Antonio, Texas, 78229, United States
The First Affiliated Hospital of Bengbu Medical College
Bengbu, Anhui, 233004, China
Anhui Provincial Hospital
Hefei, Anhui, 230000, China
The First Affiliated Hospital of Anhui Medical University
Hefei, Anhui, 230000, China
The Second Hospital of Anhui Medical University
Hefei, Anhui, 230601, China
Cancer Hospital Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, 100021, China
Military Hospital of China
Beijing, Beijing Municipality, 100039, China
Beijing Youan Hospital, Capital Medical University
Beijing, Beijing Municipality, 100069, China
Beijing Cancer Hospital
Beijing, Beijing Municipality, 100142, China
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100730, China
Chinese Pla General Hospital
Beijing, Beijing Municipality, 100853, China
The First Affiliated Hospital of Chongqing Medical University
Chongqing, Chongqing Municipality, 630014, China
Fujian Medical University Union Hospital
Fuzhou, Fujian, 350001, China
Fujian Cancer Hospital
Fuzhou, Fujian, 350014, China
Sun Yat Sen Memorial Hospital, Sun Yat Sen University (North)
Guangzhou, Guangdong, 510000, China
Guangdong Provincial Peoples Hospital
Guangzhou, Guangdong, 510080, China
The First Affiliated Hospital, Sun Yat Sen University
Guangzhou, Guangdong, 510080, China
Nanfang Hospital of Southern Medical University
Guangzhou, Guangdong, 510515, China
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, 150000, China
Henan Cancer Hospital
Zhengzhou, Henan, 450000, China
Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, 430022, China
Zhongnan Hospital of Wuhan University Wuhan
Wuhan, Hubei, 430071, China
Hubei Cancer Hospital
Wuhan, Hubei, 430079, China
General Hospital of Eastern Theater Command
Nanjing, Jiangsu, 210002, China
Jiangsu Province Cancer Hospital
Nanjing, Jiangsu, 210008, China
The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, 215006, China
The Second Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, 330006, China
Jilin Province Peoples Hospital
Changchun, Jilin, 130021, China
The First Hospital of Jilin University
Changchun, Jilin, 130021, China
The First Affiliated Hospital of Xian Jiaotong University
Xi'an, Shaanxi, 710061, China
The Affiliated Hospital of Qingdao University Branch Laoshan
Qingdao, Shandong, 266000, China
Weifang Peoples Hospital
Weifang, Shandong, 261000, China
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, 200000, China
Affiliated Zhongshan Hospital of Fudan University
Shanghai, Shanghai Municipality, 200032, China
Tianjin Medical University Cancer Institute and Hospital
Tianjin, Tianjin Municipality, 300060, China
The First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310003, China
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310016, China
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, 310022, China
Fakultni Nemocnice Brno
Brno, 62500, Czechia
Fakultni Nemocnice V Motole
Prague, 150 06, Czechia
Chu Caen Normandie
Caen, 14033, France
Hopital Beaujon
Clichy, 92210, France
Chu Besancon Hopital Jean Minjoz
Doubs, 25030, France
Chu de Grenoble Oncology
Grenoble, 38043, France
Chru de Lille Hopital Claude Huriez Hepato Gastro Enterologie
Lille, 59037, France
Chu Montpellier Hopital Saint Eloi
Montpellier, 34295, France
Centre Hospitalier Universitaire Nantes Hotel Dieu
Nantes, 44093, France
Hopital Larchet Chu Nice
Nice, 6200, France
Chu de Poitiers Site de La Mileterie
Poitiers, 86000, France
Hopital Robert Debre
Reims, 51056, France
Chu Saint Etienne Hopital Nord
Saint-Priest-en-Jarez, 42270, France
Hopital Paul Brousse Aphp
Villejuif, 94800, France
Institut Gustave Roussy
Villejuif, 94805, France
Charite Universitatsmedizin Berlin
Berlin, 13353, Germany
Universitatsklinikum Bonn
Bonn, 53127, Germany
Uniklinik Koln (Aor)
Cologne, 50937, Germany
Universitatsklinikum Dusseldorf
Düsseldorf, 40225, Germany
Kliniken Essen Mitte Evang Huyssens Stiftung
Essen, 45136, Germany
Medizinische Hochschule Hannover
Hanover, 30625, Germany
Universitaetsklinikum Leipzig Aor
Leipzig, 04103, Germany
Policlinico Sorsola Malpighi, Aou Di Bologna
Bologna, 40138, Italy
Po Di Cremona, Asst Di Cremona Oncologia Medica
Cremona, 26100, Italy
Universita Degli Studi Di Modena Azienda Ospedaliere Policlinco
Modena, 41124, Italy
Irccs Policlinico San Matteo, Universita Degli Studi Di Pavi
Pavia, 27100, Italy
Ulssdolomiti
Peschiera del Garda, 37019, Italy
Po Umberto I, Ao Ordine Mauriziano
Torino, 10128, Italy
Osp Sbortolo, Ulss Berica
Vicenza, 36100, Italy
Fujita Health University Hospital
Toyoake, Aichi-ken, 470-1192, Japan
Ehime Prefectural Central Hospital Gastroenterologic Medicine
Matsuyama, Ehime, 790-0024, Japan
National Hospital Organization Kyushu Medical Center
Fukuokacity, Fukuoka, 810-8563, Japan
Ogaki Municipal Hospital Gastroenterological Medicine
Ōgaki, Gifu, 503-8502, Japan
Hokkaido University Hospital
Sapporo, Hokkaido, 060-8648, Japan
Hyogo Medical University Hospital
Nishinomiyashi, Hyōgo, 663-8501, Japan
Kanazawa University Hospital
Kanazawa, Ishikawa-ken, 920-8641, Japan
Iwate Medical University Hospital
Yahabacho Shiwagun, Iwate, 028-3695, Japan
Yokohama City University Medical Center Gastroenterological Center
Yokohama, Kanagawa, 232-0024, Japan
Kanagawa Cancer Center
Yokohama, Kanagawa, 241-8515, Japan
National Hospital Organization Nagasaki Medical Center Gastroenterology
Ōmura, Nagasaki, 856-8562, Japan
Nho Osaka National Hospital
Osakashi, Osaka, 540-0006, Japan
Osaka International Cancer Institute
Osakashi, Osaka, 541-8567, Japan
Kindai University Hospital
Sayama, Osaka, 589-8511, Japan
Osaka University Hospital
Suitashi, Osaka, 565-0871, Japan
Sasaki Foundation Kyoundo Hospital Hepatology
Bunkyoku, Tokyo, 1138655, Japan
Nihon University Itabashi Hospital Gastroenterological Surgery
Itabashiku, Tokyo, 173-8610, Japan
Japanese Red Cross Medical Center Gastroenterology
Shibuyaku, Tokyo, 150-8935, Japan
Center Hospital of the National Center For Global Health and Medicine
Shinjukuku, Tokyo, 162-8655, Japan
Wakayama Medical University
Wakayama, Wakayama, 641-8510, Japan
Chiba University Hospital Gastroenterological Medicine
Chiba, 260-8677, Japan
Kumamoto University Hospital
Kumamoto, 860-8556, Japan
University Hospital, Kyoto Prefectural Univ of Medicine
Kyoto, 602-8566, Japan
Osaka City General Hospital
Osaka, 534-0021, Japan
Osaka Metropolitan University Hospital
Osaka, 545-8586, Japan
Tottori University Hospital Multidisciplinary Internal Medicine
Tottori, 683-8504, Japan
Uniwersyteckie Centrum Kliniczne
Gdansk, 80-952, Poland
Clinical Research Center Sp Z Oo, Medic R Sp K
Poznan, 60-569, Poland
Narodowy Instytut Onkologii Im Marii Skodowskiej Curie Pastwowy Instytut Badawczy
Warsaw, 02-034, Poland
Centrum Badan Klinicznych
Wroclaw, 51-149, Poland
Hospital Universitario Vall Dhebron
Barcelona, 08035, Spain
Institut Catala Doncologia
Barcelona, 08908, Spain
Hospital Universitario Hm Madrid Sanchinarro
Madrid, 28050, Spain
Hospital Universitari I Politecnic La Fe
Valencia, 46026, Spain
Kaohsiung Medical University Chung Ho Memorial Hospital
Kaohsiung City, 807, Taiwan
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, 83301, Taiwan
China Medical University Hospital
Taichung, 40447, Taiwan
Taichung Veterans General Hospital Gastroenterology
Taichung, 407, Taiwan
National Cheng Kung University Hospital
Tainan, 704, Taiwan
Chi Mei Medical Center
Tainan, 710, Taiwan
Taipei Veterans General Hospital
Taipei, 11217, Taiwan
Tri Service General Hospital
Taipei, 114, Taiwan
Linkou Chang Gung Memorial Hospital
Taoyuan District, 33305, Taiwan
Queen Elizabeth Hospital
Birmingham, B15 2TH, United Kingdom
The Christie Hospital
Greater Manchester, M20 4BX, United Kingdom
Royal Free Hospital London Nhs Trust
London, NW3 2QG, United Kingdom
Kings College
London, SE5 9RS, United Kingdom
Related Publications (3)
Qin S, Finn RS, Kudo M, Meyer T, Vogel A, Ducreux M, Macarulla TM, Tomasello G, Boisserie F, Hou J, Li X, Song J, Zhu AX. RATIONALE 301 study: tislelizumab versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma. Future Oncol. 2019 Jun;15(16):1811-1822. doi: 10.2217/fon-2019-0097. Epub 2019 Apr 10.
PMID: 30969136RESULTQin S, Kudo M, Meyer T, Bai Y, Guo Y, Meng Z, Satoh T, Marino D, Assenat E, Li S, Chen Y, Boisserie F, Abdrashitov R, Finn RS, Vogel A, Zhu AX. Tislelizumab vs Sorafenib as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2023 Dec 1;9(12):1651-1659. doi: 10.1001/jamaoncol.2023.4003.
PMID: 37796513RESULTFinn RS, Kudo M, Barnes G, Meyer T, Boisserie F, Abdrashitov R, Chen Y, Li S, Zhu AX, Qin S, Vogel A. Tislelizumab versus Sorafenib in First-Line Treatment of Unresectable Hepatocellular Carcinoma: Impact on Health-Related Quality of Life in RATIONALE-301 Study. Liver Cancer. 2024 Feb 21;13(5):548-560. doi: 10.1159/000537966. eCollection 2024 Oct.
PMID: 39435268RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- BeiGene
Study Officials
- STUDY DIRECTOR
Study Director, MD
BeiGene
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 3, 2018
First Posted
January 26, 2018
Study Start
December 18, 2017
Primary Completion
July 11, 2022
Study Completion
December 14, 2023
Last Updated
October 14, 2025
Results First Posted
October 14, 2025
Record last verified: 2025-09
Data Sharing
- IPD Sharing
- Will share