Hepatocellular Carcinoma (HCC)Phase 3NCT03412773
A Study of Tislelizumab Versus Sorafenib in Participants With Unresectable Hepatocellular Carcinoma (HCC)
A Phase 3 study testing Tislelizumab and Sorafenib in people with Hepatocellular Carcinoma (HCC), run by BeiGene at 122 sites in 11 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma (HCC)
- What is being tested?
- Tislelizumab and Sorafenib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 684 participants
- Where
- 122 sitesin 11 countries
- Study dates
- 18 Dec 2017to 14 Dec 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Safety Run-In Sub-study Eligibility Criteria: The study included adult Japanese participants (≥ 20 years) with histologically confirmed hepatocellular carcinoma (HCC) at Barcelona Clinic Liver Cancer (BCLC) Stage C or B. Eligible participants had either received, were ineligible for, or declined standard treatment. Additional requirements were a Child-Pugh A classification within 7 days before enrollment, at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and an Eastern Cooperative Oncology Group (ECOG) Performance Status score of ≤ 1.
Main Study Key Inclusion Criteria:
- 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
Main Study Key Exclusion Criteria:
- 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.
Trial locations and contacts
122 sites in 11 countries.
122 sites in 11 countries
China37 sites
Cancer Hospital Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, 100021
Military Hospital of China
Beijing, Beijing Municipality, 100039
Beijing Youan Hospital, Capital Medical University
Beijing, Beijing Municipality, 100069
Beijing Cancer Hospital
Beijing, Beijing Municipality, 100142
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100730
Chinese Pla General Hospital
Beijing, Beijing Municipality, 100853
The First Affiliated Hospital of Bengbu Medical College
Bengbu, Anhui, 233004
Jilin Province Peoples Hospital
Changchun, Jilin, 130021
The First Hospital of Jilin University
Changchun, Jilin, 130021
The First Affiliated Hospital of Chongqing Medical University
Chongqing, Chongqing Municipality, 630014
Fujian Medical University Union Hospital
Fuzhou, Fujian, 350001
Fujian Cancer Hospital
Fuzhou, Fujian, 350014
Sun Yat Sen Memorial Hospital, Sun Yat Sen University (North)
Guangzhou, Guangdong, 510000
Guangdong Provincial Peoples Hospital
Guangzhou, Guangdong, 510080
The First Affiliated Hospital, Sun Yat Sen University
Guangzhou, Guangdong, 510080
Nanfang Hospital of Southern Medical University
Guangzhou, Guangdong, 510515
The First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310003
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310016
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, 310022
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, 150000
Anhui Provincial Hospital
Hefei, Anhui, 230000
The First Affiliated Hospital of Anhui Medical University
Hefei, Anhui, 230000
The Second Hospital of Anhui Medical University
Hefei, Anhui, 230601
The Second Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, 330006
General Hospital of Eastern Theater Command
Nanjing, Jiangsu, 210002
Jiangsu Province Cancer Hospital
Nanjing, Jiangsu, 210008
The Affiliated Hospital of Qingdao University Branch Laoshan
Qingdao, Shandong, 266000
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, 200000
Affiliated Zhongshan Hospital of Fudan University
Shanghai, Shanghai Municipality, 200032
The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, 215006
Tianjin Medical University Cancer Institute and Hospital
Tianjin, Tianjin Municipality, 300060
Weifang Peoples Hospital
Weifang, Shandong, 261000
Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, 430022
Zhongnan Hospital of Wuhan University Wuhan
Wuhan, Hubei, 430071
Hubei Cancer Hospital
Wuhan, Hubei, 430079
The First Affiliated Hospital of Xian Jiaotong University
Xi'an, Shaanxi, 710061
Henan Cancer Hospital
Zhengzhou, Henan, 450000
Japan26 sites
Sasaki Foundation Kyoundo Hospital Hepatology
Bunkyoku, Tokyo, 1138655
Chiba University Hospital Gastroenterological Medicine
Chiba, 260-8677
National Hospital Organization Kyushu Medical Center
Fukuokacity, Fukuoka, 810-8563
Kanazawa University Hospital
Kanazawa, Ishikawa-ken, 920-8641
Kumamoto University Hospital
Kumamoto, 860-8556
University Hospital, Kyoto Prefectural Univ of Medicine
Kyoto, 602-8566
Ehime Prefectural Central Hospital Gastroenterologic Medicine
Matsuyama, Ehime, 790-0024
Hyogo Medical University Hospital
Nishinomiyashi, Hyōgo, 663-8501
Ogaki Municipal Hospital Gastroenterological Medicine
Ōgaki, Gifu, 503-8502
National Hospital Organization Nagasaki Medical Center Gastroenterology
Ōmura, Nagasaki, 856-8562
Osaka City General Hospital
Osaka, 534-0021
Osaka Metropolitan University Hospital
Osaka, 545-8586
Nho Osaka National Hospital
Osakashi, Osaka, 540-0006
Osaka International Cancer Institute
Osakashi, Osaka, 541-8567
Hokkaido University Hospital
Sapporo, Hokkaido, 060-8648
Kindai University Hospital
Sayama, Osaka, 589-8511
Japanese Red Cross Medical Center Gastroenterology
Shibuyaku, Tokyo, 150-8935
Center Hospital of the National Center For Global Health and Medicine
Shinjukuku, Tokyo, 162-8655
Osaka University Hospital
Suitashi, Osaka, 565-0871
Nihon University Itabashi Hospital Gastroenterological Surgery
tabashi City, Tokyo, 173-8610
Tottori University Hospital Multidisciplinary Internal Medicine
Tottori, 683-8504
Fujita Health University Hospital
Toyoake, Aichi-ken, 470-1192
Wakayama Medical University
Wakayama, Wakayama, 641-8510
Iwate Medical University Hospital
Yahabacho Shiwagun, Iwate, 028-3695
Yokohama City University Medical Center Gastroenterological Center
Yokohama, Kanagawa, 232-0024
Kanagawa Cancer Center
Yokohama, Kanagawa, 241-8515
France13 sites
Chu Caen Normandie
Caen, 14033
Hopital Beaujon
Clichy, 92210
Chu Besancon Hopital Jean Minjoz
Doubs, 25030
Chu de Grenoble Oncology
Grenoble, 38043
Chru de Lille Hopital Claude Huriez Hepato Gastro Enterologie
Lille, 59037
Chu Montpellier Hopital Saint Eloi
Montpellier, 34295
Centre Hospitalier Universitaire Nantes Hotel Dieu
Nantes, 44093
Hopital Larchet Chu Nice
Nice, 6200
Chu de Poitiers Site de La Mileterie
Poitiers, 86000
Hopital Robert Debre
Reims, 51056
Chu Saint Etienne Hopital Nord
Saint-Priest-en-Jarez, 42270
Hopital Paul Brousse Aphp
Villejuif, 94800
Institut Gustave Roussy
Villejuif, 94805
United States9 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Xcancerdayton Physician Network
Dayton, Ohio, 45409
Providence Medical Foundation
Fullerton, California, 92835
Rj Zuckerberg Cancer Center
Lake Success, New York, 11042
UCLA Hematologyoncology
Los Angeles, California, 90095
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Umdnj Njms
Newark, New Jersey, 07840
Chao Family Comprehensive Cancer Center
Orange, California, 92868
Ut Health San Antonio Mays Cancer Center
San Antonio, Texas, 78229
Taiwan9 sites
Kaohsiung Medical University Chung Ho Memorial Hospital
Kaohsiung City, 807
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, 83301
China Medical University Hospital
Taichung, 40447
Taichung Veterans General Hospital Gastroenterology
Taichung, 407
National Cheng Kung University Hospital
Tainan, 704
Chi Mei Medical Center
Tainan, 710
Taipei Veterans General Hospital
Taipei, 11217
Tri Service General Hospital
Taipei, 114
Linkou Chang Gung Memorial Hospital
Taoyuan, 33305
Germany7 sites
Charite Universitatsmedizin Berlin
Berlin, 13353
Universitatsklinikum Bonn
Bonn, 53127
Uniklinik Koln (Aor)
Cologne, 50937
Universitatsklinikum Dusseldorf
Düsseldorf, 40225
Kliniken Essen Mitte Evang Huyssens Stiftung
Essen, 45136
Medizinische Hochschule Hannover
Hanover, 30625
Universitaetsklinikum Leipzig Aor
Leipzig, 04103
Italy7 sites
Policlinico Sorsola Malpighi, Aou Di Bologna
Bologna, 40138
Po Di Cremona, Asst Di Cremona Oncologia Medica
Cremona, 26100
Universita Degli Studi Di Modena Azienda Ospedaliere Policlinco
Modena, 41124
Irccs Policlinico San Matteo, Universita Degli Studi Di Pavi
Pavia, 27100
Ulssdolomiti
Peschiera del Garda, 37019
Po Umberto I, Ao Ordine Mauriziano
Torino, 10128
Osp Sbortolo, Ulss Berica
Vicenza, 36100
Poland4 sites
Uniwersyteckie Centrum Kliniczne
Gdansk, 80-952
Clinical Research Center Sp Z Oo, Medic R Sp K
Poznan, 60-569
Narodowy Instytut Onkologii Im Marii Skodowskiej Curie Pastwowy Instytut Badawczy
Warsaw, 02-034
Centrum Badan Klinicznych
Wroclaw, 51-149
Spain4 sites
Hospital Universitario Vall Dhebron
Barcelona, 08035
Institut Catala Doncologia
Barcelona, 08908
Hospital Universitario Hm Madrid Sanchinarro
Madrid, 28050
Hospital Universitari I Politecnic La Fe
Valencia, 46026
United Kingdom4 sites
Queen Elizabeth Hospital
Birmingham, B15 2TH
The Christie Hospital
Greater Manchester, M20 4BX
Royal Free Hospital London Nhs Trust
London, NW3 2QG
Kings College
London, SE5 9RS
Czechia2 sites
Fakultni Nemocnice Brno
Brno, 62500
Fakultni Nemocnice V Motole
Prague, 150 06
About this study
Official title: 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
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.
- Conditions
- Hepatocellular Carcinoma (HCC)
- Being tested
- Tislelizumab, Sorafenib
- Keywords
- Advanced liver cancer, RATIONALE-301
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TislelizumabDrug
Also called BGB-A317
Tislelizumab 200 mg intravenously (IV) once every three weeks (Q3W)
SorafenibDrug
Also called Nexavar, BAY43-9006
Sorafenib 400 mg orally (PO) twice daily (BID)
| Study group | Role | What they receive |
|---|---|---|
| Safety Run-In Sub-study | Experimental | Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability. Receives: Drug: Tislelizumab |
| Arm A: Tislelizumab | Experimental | Participants 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. Receives: Drug: Tislelizumab |
| Arm B: Sorafenib | Active comparator | Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit. Receives: Drug: Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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.
Measured: 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)
Defined as the percentage of participants who had partial response or complete response as determined by Blinded Independent Review Committee (BIRC) per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in all randomized participants with measurable disease at baseline.
ORR was not assessed by the BIRC for participants in the sub-study, and this was not a pre-specified sub-study endpoint.
Measured: 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
Defined as the percentage of participants who had partial response or complete response as determined by the investigator per RECIST v1.1 in all randomized participants with measurable disease at baseline.
Measured: 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
Defined as the time from randomization to the first objectively documented disease progression, or death from any cause, whichever occurred first, as assessed by the BIRC per RECIST v1.1. Kaplan-Meier methodology was used to estimate the median PFS.
PFS was not assessed by the BIRC for participants in the sub-study, and this was not a pre-specified sub-study endpoint.
Measured: 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
Defined as the time from randomization to the first objectively documented disease progression, or death from any cause, whichever occurred first, as assessed by the investigator per RECIST v1.1. Kaplan-Meier methodology was used to estimate the median PFS.
Measured: 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
Defined as the time from the first occurrence of a documented objective response until the first documentation of progression or death from any cause, whichever occurred first, as determined by the BIRC per RECIST v1.1. Median DOR was estimated using Kaplan-Meier methodology.
DOR was not assessed by the BIRC for participants in the sub-study, and this was not a pre-specified sub-study endpoint.
Measured: Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months)
Duration of Response (DOR) Assessed by the Investigator
Defined as the time from the first occurrence of a documented objective response until the first documentation of progression or death from any cause, whichever occurred first, as assessed by the investigator per RECIST v1.1. Median DOR was estimated using Kaplan-Meier methodology.
Measured: Through the study completion data cut-off date of December 14th, 2023 (up to approximately 65 months)
Time to Progression (TTP) Assessed by BIRC
Defined as the time from the date of randomization to the date of the first objectively documented tumor progression as assessed by the BIRC per RECIST v1.1. Median TTP was estimated using Kaplan-Meier methodology.
TTP was not assessed by the BIRC for participants in the sub-study, and this was not a pre-specified sub-study endpoint.
Measured: Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months)
Time to Progression (TTP) as Assessed by the Investigator
Defined as the time from the date of randomization to the date of the first objectively documented tumor progression as assessed by the investigator per RECIST v1.1. Median TTP was estimated using Kaplan-Meier methodology.
TTP was not a pre-specified sub-study endpoint.
Measured: Through the study completion data cut-off date of December 14th, 2023 (up to approximately 65 months)
Safety Run-in Sub-study: Overall Survival
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.
Measured: Up a to 64 months
Disease Control Rate (DCR) as Assessed by BIRC
Defined as the percentage of participants whose best overall response (BOR) was complete response, partial response, or stable disease as assessed by the BIRC per RECIST v1.1.
DCR was not a pre-specified endpoint for participants in the sub-study.
Measured: Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months)
Disease Control Rate (DCR) as Assessed by the Investigator
Defined as the percentage of participants whose best overall response (BOR) was complete response, partial response, or stable disease as assessed by the investigator per RECIST v1.1.
DCR was not a pre-specified endpoint for participants in the sub-study.
Measured: Through the study completion data cut-off date of December 14th, 2023 (up to approximately 65 months)
Clinical Benefit Rate (CBR) as Assessed by BIRC
Defined as the percentage of participants whose best overall response (BOR) was complete response, partial response, or stable disease greater than or equal to 24 weeks in duration, as assessed by the BIRC per RECIST v1.1.
CBR was not a pre-specified endpoint for participants in the sub-study.
Measured: Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months)
Clinical Benefit Rate (CBR) as Assessed by the Investigator
Defined as the percentage of participants whose best overall response (BOR) is complete response, partial response, or stable disease greater than or equal to 24 weeks in duration, as assessed by the investigator per RECIST v1.1.
CBR was not a pre-specified endpoint for participants in the sub-study.
Measured: Through the study completion data cut-off date of December 14th, 2023 (up to approximately 65 months)
Change From Baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Hepatocellular Carcinoma 18 Questions (EORTC QLQ HCC 18) Index Score at Cycle 4
The EORTC QLQ-HCC18 is a questionnaire specifically designed to assess health-related quality of life in participants with hepatocellular carcinoma. It includes six symptom scales measuring Fatigue (3 items), Jaundice (2 items), Body Image (2 items), Nutrition (5 items), Pain (2 items), Fever (2 items) and two single items measuring Sex Life and Abdominal Swelling. Participants respond on a scale from 1 = "Not at all" to 4 = "Very Much. Raw scores are transformed into a 0 to 100 scale using linear transformation. The HCC18 Index score is calculated from each of the 6 symptom scales and the 2 single items, and ranges from 0 to 100. Higher scores indicate greater symptom burden or worse quality of life.
The EORTC QLQ-HCC18 was not assessed for participants in the sub-study.
Measured: Baseline to Cycle 4 (each cycle was 21 days)
Change From Baseline in the European EORTC QLQ HCC 18 Index Score at Cycle 6
The EORTC QLQ-HCC18 is a questionnaire specifically designed to assess health-related quality of life in participants with hepatocellular carcinoma. It includes six symptom scales measuring Fatigue (3 items), Jaundice (2 items), Body Image (2 items), Nutrition (5 items), Pain (2 items), Fever (2 items) and two single items measuring Sex Life and Abdominal Swelling. Participants respond on a scale from 1 = "Not at all" to 4 = "Very Much. Raw scores are transformed into a 0 to 100 scale using linear transformation. The HCC18 Index score is calculated from each of the 6 symptom scales and the 2 single items, and ranges from 0 to 100. Higher scores indicate greater symptom burden or worse quality of life.
The HEORTC QLQ-HCC18 was not assessed in participants in the sub-study.
Measured: Baseline to Cycle 6 (Each cycle was 21 days)
Change From Baseline in the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life Score at Cycle 4
The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of participants with cancer. It includes global health status and quality of life questions related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes.
The EORTC QLQ-C30 was not assessed in participants in the sub-study.
Measured: Baseline to Cycle 4 (each cycle was 21 days)
Change From Baseline in the EORTC QLQ-C30 Global Health Status/Quality of Life Score at Cycle 6
The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of participants with cancer. It includes global health status and quality of life questions related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes.
The EORTC QLQ-C30 was not assessed in participants in the sub-study.
Measured: Baseline to Cycle 6 (each cycle was 21 days)
Change From Baseline in the European Quality of Life 5 Dimensions, 5-level (EQ-5D-5L) Visual Analogue Scale (VAS) at Cycle 4
The EQ-5D-5L comprises a descriptive module and a Visual Analogue scale (VAS). The EQ-5D-5L VAS measures respondent's self-rated health status on a 0 to 100 scale, with 100 = 'the best health you can imagine' and 0 = 'the worst health you can imagine'. Higher scores on VAS indicate higher health status.
The EQ-5D-5L VAS was not assessed in participants in the sub-study.
Measured: Baseline to Cycle 4 (each cycle was 21 days)
Change From Baseline in the EQ-5D-5L VAS at Cycle 6
The EQ-5D-5L comprises a descriptive module and a visual analogue scale (VAS). The EQ-5D-5L VAS measures respondent's self-rated health status on a 0 to 100 scale, with 100 = 'the best health you can imagine' and 0 = 'the worst health you can imagine'. Higher scores on VAS indicate higher health status.
The EQ-5D-5L VAS was not assessed in participants in the sub-study.
Measured: Baseline to Cycle 6 (each cycle was 21 days)
Main Study: Number of Participants With Treatment-emergent Adverse Events
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).
Measured: From the first dose to 30 days after the last dose, new anticancer therapy, or the study completion analysis cutoff on December 14th, 2023 (a maximum of 61 months for participants in Arm A and 63 months for participants in Arm B).
Safety Run-in Sub-study: Number of Participants Who Developed Anti-tislelizumab Antibodies
Treatment-emergent anti-drug antibodies (ADA): participants who were ADA negative at baseline and ADA positive post-baseline.
Treatment-boosted ADA: participants who were ADA positive at baseline that was boosted to a 4-fold or higher-level following drug administration.
ADA assessments were not performed for participants enrolled in the main study.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2018
- Study start18 Dec 2017
- Primary completion11 Jul 2022
- Study completion14 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular Carcinoma (HCC)Studies of the same condition, open and under way.
- More trials run by BeiGeneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 684 participants (actual)
Sponsor and investigators
- Lead sponsor
- BeiGene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, MD, Study director, BeiGene
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03412773
- Sponsor's protocol ID
- BGB-A317-301
- Other IDs
- 2017-002423-19, CTR20170882, JapicCTI-194569, RATIONALE-301, 2017
- Status last verified
- Sep 2025
- First submitted
- 3 Jan 2018
- Last updated
- 14 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
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.
PubMed 30969136Qin 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.
PubMed 37796513Finn 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.
PubMed 39435268
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03412773
- Acronym / sponsor ID
- BGB-A317-301
- Conditions
- Hepatocellular Carcinoma (HCC)
- Keywords
- Advanced liver cancer, RATIONALE-301
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 684 participants (actual)
- Lead sponsor
- BeiGeneIndustry (pharma, biotech, devices)
- Study start
- 18 Dec 2017 (actual)
- Primary completion
- 11 Jul 2022 (actual)
- Study completion
- 14 Dec 2023 (actual)
- First posted
- 26 Jan 2018 (actual)
- Results
- Posted 14 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Safety Run-In Sub-study | Experimental | Drug: TislelizumabJapanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability. |
| Arm A: Tislelizumab | Experimental | Drug: TislelizumabParticipants 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 comparator | Drug: SorafenibParticipants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TislelizumabAlso: BGB-A317Tislelizumab 200 mg intravenously (IV) once every three weeks (Q3W) | Drug | Arm A: Tislelizumab, Safety Run-In Sub-study |
| SorafenibAlso: Nexavar, BAY43-9006Sorafenib 400 mg orally (PO) twice daily (BID) | Drug | Arm B: Sorafenib |
Primary outcome
Safety Run-in Sub-study: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: 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)
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).
Safety Run-in Sub-study: Serum Concentration of Tislelizumab
Time frame: 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).
Serum concentration of tislelizumab was a pre-specified primary endpoint for the sub-study only.
Main Study: Overall Survival (OS)
Time frame: Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months)
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.
21 secondary outcomes
Overall Response Rate (ORR) as Assessed by Blinded Independent Review Committee (BIRC)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months)
Duration of Response (DOR) Assessed by the Investigator
Time frame: Through the study completion data cut-off date of December 14th, 2023 (up to approximately 65 months)
Time to Progression (TTP) Assessed by BIRC
Time frame: Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months)
Time to Progression (TTP) as Assessed by the Investigator
Time frame: Through the study completion data cut-off date of December 14th, 2023 (up to approximately 65 months)
Safety Run-in Sub-study: Overall Survival
Time frame: Up a to 64 months
Disease Control Rate (DCR) as Assessed by BIRC
Time frame: Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months)
Disease Control Rate (DCR) as Assessed by the Investigator
Time frame: Through the study completion data cut-off date of December 14th, 2023 (up to approximately 65 months)
Clinical Benefit Rate (CBR) as Assessed by BIRC
Time frame: Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months)
Clinical Benefit Rate (CBR) as Assessed by the Investigator
Time frame: Through the study completion data cut-off date of December 14th, 2023 (up to approximately 65 months)
Change From Baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Hepatocellular Carcinoma 18 Questions (EORTC QLQ HCC 18) Index Score at Cycle 4
Time frame: Baseline to Cycle 4 (each cycle was 21 days)
Change From Baseline in the European EORTC QLQ HCC 18 Index Score at Cycle 6
Time frame: Baseline to Cycle 6 (Each cycle was 21 days)
Change From Baseline in the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life Score at Cycle 4
Time frame: Baseline to Cycle 4 (each cycle was 21 days)
Change From Baseline in the EORTC QLQ-C30 Global Health Status/Quality of Life Score at Cycle 6
Time frame: Baseline to Cycle 6 (each cycle was 21 days)
Change From Baseline in the European Quality of Life 5 Dimensions, 5-level (EQ-5D-5L) Visual Analogue Scale (VAS) at Cycle 4
Time frame: Baseline to Cycle 4 (each cycle was 21 days)
Change From Baseline in the EQ-5D-5L VAS at Cycle 6
Time frame: Baseline to Cycle 6 (each cycle was 21 days)
Main Study: Number of Participants With Treatment-emergent Adverse Events
Time frame: From the first dose to 30 days after the last dose, new anticancer therapy, or the study completion analysis cutoff on December 14th, 2023 (a maximum of 61 months for participants in Arm A and 63 months for participants in Arm B).
Safety Run-in Sub-study: Number of Participants Who Developed Anti-tislelizumab Antibodies
Time frame: 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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 30969136Qin 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.
- Results publication: PubMed 37796513Qin 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.
- Results publication: PubMed 39435268Finn 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.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director, MD study director
BeiGene
122 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tislelizumab and Sorafenib in people with Hepatocellular Carcinoma (HCC), run by BeiGene at 122 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 122 sites in China, Japan, France, United States, Taiwan and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety Run-in Sub-study: Number of Participants With Treatment-emergent Adverse Events (TEAEs) (time frame: 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)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03412773, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2025.