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

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 Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma (HCC)
• Intervention / Treatment: Drug: Tislelizumab; Drug: Sorafenib

• Study Type: Interventional
• Enrollment (Actual): 684
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China, 233004
      • The First Affiliated Hospital of Bengbu Medical College
    • Hefei, Anhui, China, 230000
      • The First Affiliated Hospital of Anhui Medical University
    • Hefei, Anhui, China, 230601
      • The second hospital of Anhui medical university
    • Hefei, Anhui, China, 230000
      • Anhui Provincial Hospital
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100853
      • Chinese PLA General Hospital
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing Municipality, China, 100021
      • Cancer Hospital Chinese Academy of Medical Sciences
    • Beijing, Beijing Municipality, China, 100730
      • Peking Union Medical College Hospital
    • Beijing, Beijing Municipality, China, 100039
      • Military Hospital of China
    • Beijing, Beijing Municipality, China, 100069
      • Beijing Youan Hospital, Capital Medical University
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 630014
      • The First Affiliated Hospital of Chongqing Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Fujian Medical University Union Hospital
    • Fuzhou, Fujian, China, 350014
      • Fujian Cancer Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Provincial Peoples Hospital
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital of Southern Medical University
    • Guangzhou, Guangdong, China, 510000
      • Sun Yat Sen Memorial Hospital, Sun Yat Sen University (North)
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital, Sun Yat Sen University
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Harbin medical university cancer hospital
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital
    • Wuhan, Hubei, China, 430022
      • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
    • Wuhan, Hubei, China, 430071
      • Zhongnan Hospital of Wuhan University Wuhan
  • Jiangsu
    • Nanjing, Jiangsu, China, 210002
      • General Hospital of Eastern Theater Command
    • Nanjing, Jiangsu, China, 210008
      • Jiangsu Province Cancer Hospital
    • Suzhou, Jiangsu, China, 215006
      • The First Affiliated Hospital of Soochow University
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The Second Affiliated Hospital of Nanchang University
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
    • Changchun, Jilin, China, 130021
      • Jilin Province Peoples Hospital
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • The First Affiliated Hospital of Xian Jiaotong University
  • Shandong
    • Qingdao, Shandong, China, 266000
      • The Affiliated Hospital of Qingdao University Branch Laoshan
    • Weifang, Shandong, China, 261000
      • Weifang Peoples Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200000
      • Fudan University Shanghai Cancer Center
    • Shanghai, Shanghai Municipality, China, 200032
      • Affiliated Zhongshan Hospital of Fudan University
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China, 310003
      • The first Affiliated Hospital, Zhejiang University School of Medicine
• Czechia
  • Brno, Czechia, 62500
    • Fakultni nemocnice Brno
  • Prague, Czechia, 150 06
    • Fakultni nemocnice v Motole
• France
  • Caen, France, 14033
    • CHU Caen Normandie
  • Clichy, France, 92210
    • Hopital Beaujon
  • Doubs, France, 25030
    • CHU Besançon Hopital Jean Minjoz
  • Grenoble, France, 38043
    • Chu de Grenoble Oncology
  • Lille, France, 59037
    • Chru de Lille Hopital Claude Huriez Hepato Gastro Enterologie
  • Montpellier, France, 34295
    • Chu Montpellier Hopital Saint Eloi
  • Nantes, France, 44093
    • Centre Hospitalier Universitaire Nantes Hotel Dieu
  • Nice, France, 6200
    • Hopital Larchet Chu Nice
  • Poitiers, France, 86000
    • Chu de Poitiers Site de La Mileterie
  • Reims, France, 51056
    • Hôpital Robert Debré
  • Saint-Priest-en-Jarez, France, 42270
    • CHU Saint Etienne Hopital Nord
  • Villejuif, France, 94805
    • Institut Gustave Roussy
  • Villejuif, France, 94800
    • Hôpital Paul Brousse APHP
• Germany
  • Berlin, Germany, 13353
    • Charité Universitätsmedizin Berlin
  • Bonn, Germany, 53127
    • Universitatsklinikum Bonn
  • Cologne, Germany, 50937
    • Uniklinik Koln (Aor)
  • Düsseldorf, Germany, 40225
    • Universitatsklinikum Dusseldorf
  • Essen, Germany, 45136
    • Kliniken Essen Mitte Evang Huyssens Stiftung
  • Hanover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Leipzig, Germany, 04103
    • Universitaetsklinikum Leipzig Aor
• Italy
  • Bologna, Italy, 40138
    • Policlinico Sorsola Malpighi, Aou Di Bologna
  • Cremona, Italy, 26100
    • Po Di Cremona, Asst Di Cremona Oncologia Medica
  • Modena, Italy, 41124
    • Universita Degli Studi Di Modena Azienda Ospedaliere Policlinco
  • Pavia, Italy, 27100
    • IRCCS Policlinico San Matteo, Università degli studi di Pavi
  • Peschiera del Garda, Italy, 37019
    • Ulssdolomiti
  • Torino, Italy, 10128
    • Po Umberto I, Ao Ordine Mauriziano
  • Vicenza, Italy, 36100
    • Osp Sbortolo, Ulss Berica
• Japan
  • Chiba, Japan, 260-8677
    • Chiba University Hospital Gastroenterological Medicine
  • Kumamoto, Japan, 860-8556
    • Kumamoto University Hospital
  • Kyoto, Japan, 602-8566
    • University Hospital, Kyoto Prefectural Univ of Medicine
  • Osaka, Japan, 545-8586
    • Osaka Metropolitan University Hospital
  • Osaka, Japan, 534-0021
    • Osaka City General Hospital
  • Tottori, Japan, 683-8504
    • Tottori University Hospital Multidisciplinary Internal Medicine
  • Aichi-ken
    • Toyoake, Aichi-ken, Japan, 470-1192
      • Fujita Health University Hospital
  • Ehime
    • Matsuyama, Ehime, Japan, 790-0024
      • Ehime Prefectural Central Hospital Gastroenterologic Medicine
  • Fukuoka
    • Fukuokacity, Fukuoka, Japan, 810-8563
      • National Hospital Organization Kyushu Medical Center
  • Gifu
    • Ōgaki, Gifu, Japan, 503-8502
      • Ogaki Municipal Hospital Gastroenterological Medicine
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital
  • Hyōgo
    • Nishinomiyashi, Hyōgo, Japan, 663-8501
      • Hyogo Medical University Hospital
  • Ishikawa-ken
    • Kanazawa, Ishikawa-ken, Japan, 920-8641
      • Kanazawa University Hospital
  • Iwate
    • Yahabacho Shiwagun, Iwate, Japan, 028-3695
      • Iwate Medical University Hospital
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 241-8515
      • Kanagawa Cancer Center
    • Yokohama, Kanagawa, Japan, 232-0024
      • Yokohama City University Medical Center Gastroenterological Center
  • Nagasaki
    • Ōmura, Nagasaki, Japan, 856-8562
      • National Hospital Organization Nagasaki Medical Center Gastroenterology
  • Osaka
    • Osakashi, Osaka, Japan, 541-8567
      • Osaka International Cancer Institute
    • Osakashi, Osaka, Japan, 540-0006
      • NHO Osaka National Hospital
    • Sayama, Osaka, Japan, 589-8511
      • Kindai University Hospital
    • Suitashi, Osaka, Japan, 565-0871
      • Osaka University Hospital
  • Tokyo
    • Bunkyoku, Tokyo, Japan, 1138655
      • Sasaki Foundation Kyoundo Hospital Hepatology
    • Itabashiku, Tokyo, Japan, 173-8610
      • Nihon University Itabashi Hospital Gastroenterological Surgery
    • Shibuyaku, Tokyo, Japan, 150-8935
      • Japanese Red Cross Medical Center Gastroenterology
    • Shinjukuku, Tokyo, Japan, 162-8655
      • Center Hospital of the National Center for Global Health and Medicine
  • Wakayama
    • Wakayama, Wakayama, Japan, 641-8510
      • Wakayama Medical University
• Poland
  • Gdansk, Poland, 80-952
    • Uniwersyteckie Centrum Kliniczne
  • Poznan, Poland, 60-569
    • Clinical Research Center Sp Z Oo, Medic R Sp K
  • Warsaw, Poland, 02-034
    • Narodowy Instytut Onkologii Im Marii Skodowskiej Curie Pastwowy Instytut Badawczy
  • Wroclaw, Poland, 51-149
    • Centrum Badan Klinicznych
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall dHebron
  • Barcelona, Spain, 08908
    • Institut Catala Doncologia
  • Madrid, Spain, 28050
    • Hospital Universitario Hm Madrid Sanchinarro
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
• Taiwan
  • Kaohsiung City, Taiwan, 83301
    • Kaohsiung Chang Gung Memorial Hospital
  • Kaohsiung City, Taiwan, 807
    • Kaohsiung Medical University Chung Ho Memorial Hospital
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taichung, Taiwan, 407
    • Taichung Veterans General Hospital Gastroenterology
  • Tainan City, Taiwan, 704
    • National Cheng Kung University Hospital
  • Tainan City, Taiwan, 710
    • Chi Mei Medical Center
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 114
    • Tri Service General Hospital
  • Taoyuan District, Taiwan, 33305
    • Linkou Chang Gung Memorial Hospital
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Queen Elizabeth Hospital
  • Greater Manchester, United Kingdom, M20 4BX
    • The Christie Hospital
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital London Nhs Trust
  • London, United Kingdom, SE5 9RS
    • Kings College
• United States
  • California
    • Fullerton, California, United States, 92835
      • Providence Medical Foundation
    • Los Angeles, California, United States, 90095
      • UCLA Hematologyoncology
    • Orange, California, United States, 92868
      • Chao Family Comprehensive Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New Jersey
    • Newark, New Jersey, United States, 07840
      • Umdnj Njms
  • New York
    • Lake Success, New York, United States, 11042
      • Rj Zuckerberg Cancer Center
  • Ohio
    • Dayton, Ohio, United States, 45409
      • Xcancerdayton Physician Network
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • San Antonio, Texas, United States, 78229
      • UT Health San Antonio Mays Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

1. Histologically confirmed diagnosis of HCC
2. 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
3. No prior systemic therapy for HCC (with the exception of HCC participants enrolled in the safety run-in substudy [Japan only])
4. Measurable disease
5. Child-Pugh score A
6. Easter Cooperative Oncology Group (ECOG) Performance Status ≤ 1
7. Adequate organ function

Main Study Key Exclusion Criteria:

1. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC histology
2. Tumor thrombus involving main trunk of portal vein or inferior vena cava
3. Loco-regional therapy to the liver within 28 days before randomization
4. Clinical evidence of portal hypertension with bleeding esophageal or gastric varices at Screening, or within 6 months before randomization
5. 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
6. Presence at Screening of active immune deficiency or autoimmune disease and/or prior history of any immune deficiency or autoimmune disease that may relapse
7. 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
8. History of interstitial lung disease or non-infectious pneumonitis, unless induced by radiation therapy
9. 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Safety Run-In Sub-study; Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.	Drug: Tislelizumab; Tislelizumab 200 mg intravenously (IV) once every three weeks (Q3W); Other Names: BGB-A317
Experimental: Arm A: Tislelizumab; 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.	Drug: Tislelizumab; Tislelizumab 200 mg intravenously (IV) once every three weeks (Q3W); Other Names: BGB-A317
Active Comparator: Arm B: Sorafenib; Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.	Drug: Sorafenib; Sorafenib 400 mg orally (PO) twice daily (BID); Other Names: Nexavar; BAY43-9006

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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).	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.	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)

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Study Director: Study Director, MD, BeiGene

Publications and helpful links

General 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.
• Qin 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.
• Finn 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2017
• Primary Completion (Actual): July 11, 2022
• Study Completion (Actual): December 14, 2023

Study Registration Dates

• First Submitted: January 3, 2018
• First Submitted That Met QC Criteria: January 21, 2018
• First Posted (Actual): January 26, 2018

Study Record Updates

• Last Update Posted (Estimated): October 14, 2025
• Last Update Submitted That Met QC Criteria: September 24, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Advanced liver cancer; RATIONALE-301
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Amides; Benzene Derivatives; Urea; Acids, Heterocyclic; Phenylurea Compounds; Niacinamide; Nicotinic Acids; Sorafenib; tislelizumab
• Other Study ID Numbers: BGB-A317-301; 2017-002423-19 (EudraCT Number); CTR20170882 (Registry Identifier: ChinaDrugTrials); JapicCTI-194569 (Registry Identifier: Japic); RATIONALE-301 (Other Identifier: BeiGene)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No