Phase 3 Study of Tislelizumab Versus Sorafenib in Participants With Unresectable HCC

Hepatocellular Carcinoma (HCC) Clinical Trial

Official title:

RATIONALE-301: 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03412773
• Other study ID #: BGB-A317-301
• Secondary ID: 2017-002423-19CT
• Status: Completed
• Phase: Phase 3
• Start date: December 28, 2017
• Est. completion date: December 14, 2023

Study information

• Verified date: January 2024
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 674
• Est. completion date: December 14, 2023
• Est. primary completion date: July 11, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma (HCC)

Intervention

Drug:
• Tislelizumab
200 mg once every 3 weeks (Q3W), intravenous dosing (IV)
• Sorafenib
400 mg twice daily (BID), oral dosing

Locations

Country	Name	City	State
China	302 Military Hospital of China	Beijing	Beijing
China	Beijing Cancer Hospital	Beijing	Beijing
China	Beijing YouAn Hospital, Capital Medical University	Beijing	Beijing
China	Cancer Hopital Chinese Academy of Medical Sciences	Beijing	Beijing
China	Chinese PLA General Hospital	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing
China	The First Affiliated Hospital of Bengbu Medical College	Bengbu	Anhui
China	Jilin Cancer Hospital	Changchun	Jilin
China	The First Hospital of Jilin University	Changchun	Jilin
China	The First Affiliated Hospital of Chongqing Medical University	Chongqing
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Fujian Provincial Cancer Hospital	Fuzhou	Fujian
China	Guangdong General Hospital	Guangzhou	Guangdong
China	Nanfang Hospital	Guangzhou	Guangdong
China	Sun Yat-sen Memorial Hospital , Sun Yat-sen University	Guangzhou	Guangdong
China	The First Affiliated Hospital, Sun Yat-sen University	Guangzhou	Guangdong
China	Sir Run Run Shaw Hospital, Zhejiang University	Hangzhou	Zhejiang
China	The First Affiliated Hospital of Zhejiang University	HangZhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Anhui Medical University - The Second Hospital	Hefei	Anhui
China	Anhui Provincial Hospital	Hefei	Anhui
China	The First Affiliated Hospital Of Anhui Medical University	Hefei	Anhui
China	The Second Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Jiangsu Cancer Hospital	Nanjing	Jiangsu
China	Nanjing Bayi Hospital	Nanjing	Jiangsu
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	The Affiliated Hospital Of Qingdao University	Qingdao	Shandong
China	Shanghai Cancer Hospital of Fudan University	Shanghai	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai	Shanghai
China	Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital	Sichuan	Sichuan
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin
China	Weifang People's Hospital	Weifang	Shandong
China	Hubei Cancer Hospital	Wuhan	Hubei
China	Wuhan Union Hospital	Wuhan	Hubei
China	Zhongnan Hospital of Wuhan University	Wuhan	Wuhan
China	The First Affiliated Hospital Of XI'AN Jiaotong University	Xian	Shanxi
China	Henan Cancer Hospital	Zhengzhou	Henan
Czechia	Fakultni nemocnice Brno	Brno	Brno-Mesto
Czechia	Fakultni nemocnice Olomouc	Olomouc
Czechia	Fakultni nemocnice v Motole	Praha 5
France	Hospitalier Jean Minjoz	Besançon	Franche-Comté
France	CHU Saint Eloi - Pôle Digestif	Bretagne	Rennes Cedex
France	CHU Cote De Nacre - Hepato-Gastro-Enterologie Et N	Caen, Cedex 05	Basse-Normandie
France	Bichat-Beaujon Service Inter Hospitalier De Cancerologie	Clichy Cedex	Lie-de-France
France	CHU de Grenoble Alpes	La Tronche	Isere
France	CHRU De Lille - Hôpital Claude Huriez	Lille	Nord
France	CHU Nantes -hopital hotel Dieu	Nantes	Loire-Atlantique
France	CHU de Nice - Hôpital de l'Archet II	Nice	Provence-Alpes-Côte-d'Azur
France	Hôpital Privé des Côtes d'Armor - Service oncologie	Plérin	Bretagne
France	Hospital of Poitiers	Poitiers	Vienne
France	CHU Saint Etienne	Rahon	Lyon
France	Hopital Robert DEBRE, CHU Reims	Reims	Champagne-Ardenne
France	CHU Amiens-Hopital Nord - Hépato-Gastroentérologie	Somme	Amiens
France	Gustave Roussy - Medical Oncology	Villejuif	Val-de-Marne
France	Hopital Paul Brousse- Aphp Hopitaux Universitairees Paris Su	Villejuif	Lie-de-France
Germany	Maria Gonzalez-Carmona	Bonn	Nordrhein-Westfalen
Germany	Universitätsklinikum Düsseldorf	Düsseldorf
Germany	Stefan Pluntke	Essen	Nordrhein-Westfalen
Germany	Krankenhaus Nordwest gGmbH	Frankfurt/Main	Hessen
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitätsklinikum Köln	Köln
Germany	Universitätsklinikum Leipzig AöR	Leipzig
Germany	Universitätsmedizin Mainz	Mainz
Italy	Policlinico S.Orsola Malpighi, AOU di Bologna - SSD Malattie	Bologna
Italy	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	Medical Oncology	Feltre	Belluno
Italy	Ospedale Vito Fazzi, ASL Lecce	Lecce
Italy	AOU Policlinico di Modena	Modena
Italy	IRCCS Policlinico San Matteo	Pavia
Italy	Ist. Clinici Scientifici Maugeri - Unità Operativa di Oncologia	Pavia
Italy	Regina Elena, Istituto Nazionale dei Tumori, IFO, IRCCS	Roma
Italy	PO Umberto I, AO Ordine Mauriziano	Torino
Italy	Ospedale S.Bortolo, AULSS n.6 Vicenza	Vicenza	Veneto
Japan	Chiba University Hospital	Chiba	Tiba [Chiba]
Japan	Sasaki Foundation Kyoundo Hospital	Chiyoda-Ku	Tokyo
Japan	Kyushu Medical Center	Fukuoka
Japan	Nihon University Itabashi Hospital - Gastroenterological surgery	Itabashi-ku	Tôkyô [Tokyo]
Japan	Kanazawa University Hospital	Kanazawa-shi	Isikawa [Ishikawa]
Japan	Kumamoto University Hospital	Kumamoto
Japan	University Hospital, Kyoto Prefectural Univ of Medicine	Kyoto-shi	Kyôto [Kyoto]
Japan	Ehime Prefectural Central Hospital - Gastroenterology	Matsuyama	Ehime
Japan	Iwate Medical University Hospital	Morioka
Japan	Hyogo College of Medicine Hospital	Nishinomiya-shi
Japan	Ogaki Municipal Hospital	Ogaki	Gihu [Gifu]
Japan	Nagasaki Medical Center	Omura	Nagasaki
Japan	Osaka City General Hospital	Osaka	Ôsaka [Osaka]
Japan	Osaka City University Hospital	Osaka	Ôsaka [Osaka]
Japan	Osaka International Cancer Institute	Osaka
Japan	Osaka National Hospital	Osaka	Ôsaka [Osaka]
Japan	Kinki University Hospital, Faculty of Medicine - Hematology & Clinical Oncology	Osaka-sayama	Osaka
Japan	Hokkaido University Hospital - Gastroenterology	Sapporo	Hokkaidô [Hokkaido]
Japan	JRC Medical Center	Shibuya-ku	Tôkyô [Tokyo]
Japan	National Center for Global Health and Medicine	Shinjuku-ku	Tôkyô [Tokyo]
Japan	Osaka University Hospital	Suita	Osaka
Japan	Tottori University Hospital	Tottori
Japan	Fujita Health University Hospital	Toyoake	Aiti [Aichi]
Japan	Wakayama Medical University	Wakayama-shi
Japan	Kanagawa Cancer Center	Yokohama	Kanagawa
Japan	Yokohama City University Medical Center	Yokohama	Kanagawa
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Clinical Research Center Sp. z o.o., Medic-R Sp. K.	Poznan	Wielkopolskie
Poland	Centrum Onkologii Instytut im. M. Sklodowskiej-Curie	Warszawa	Mazowieckie
Poland	Wojewodzki Szpital Specjalistyczny im. Gromkowskiego we Wroclawiu	Wroclaw
Spain	Hospital Universitario Vall d'Hebrón	Barcelona
Spain	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 Universitari i Politecnic La Fe	Valencia
Taiwan	Chang Gung Medical Foundation - Kaohsiung Chang Gung Memorial Hospital - Gastroenterology	Kaohsiung
Taiwan	Kaohsiung Medical University - Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	Tri-Service General Hospital - Neihu Branch	New Taipei
Taiwan	China Medical University Hospital - Transplantology - Taichung	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	Chi Mei Medical Center - YongKang	Tainan
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Chang Gung Medical Foundation - LinKou Chang Gung Memorial Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
United Kingdom	Queen Elizabeth Hospital - Clinical Reasearch	Birmingham
United Kingdom	King's College Hospital NHS Foundation Trust	London
United Kingdom	Royal Free Hospital London NHS Trust	London
United Kingdom	The Christie NHS Foundation Trust - Oak Road Treatment Centre	Withington
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Southern California Research Center	Coronado	California
United States	St. Jude Heritage Healthcare	Fullerton	California
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Precision Cancer Research / Dayton Physicians Network	Kettering	Ohio
United States	Northwell Health/Monter Cancer Center	Lake Success	New York
United States	University of California - Hematology and Oncology	Los Angeles	California
United States	Vanderbilt University Medical Center (VUMC)	Nashville	Tennessee
United States	Ochsner Medical Center (OMC) - New Orleans ACCRU Network Sit	New Orleans	Louisiana
United States	University Medical Center New Orleans	New Orleans	Louisiana
United States	Umdnj-Njms	Newark	New Jersey
United States	Chao Family Comprehensive Cancer Center	Orange	California
United States	Cancer Treatment Centers of America - Oncology	Philadelphia	Pennsylvania
United States	Hahnemann University Hospital - Gastroenterology Hepatology	Philadelphia	Pennsylvania
United States	Inland Empire Liver Foundation	Rialto	California
United States	The Mays Cancer Center	San Antonio	Texas
United States	Healthcare Research Network III, LLC	Tinley Park	Illinois
United States	White Plains Hospital Center for Cancer Care - Oncology	White Plains	New York
United States	UMass Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Countries where clinical trial is conducted

United States,  China,  Czechia,  France,  Germany,  Italy,  Japan,  Poland,  Spain,  Taiwan,  United Kingdom, 

References & Publications (1)

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. 2 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)		From date of randomization up to 4 years, approximately
Primary	Safety Run-In Substudy[Japan only]: Percentage of participants with adverse events		From date of enrollment up to 4 years, approximately.
Primary	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].
Primary	Safety Run-In Substudy[Japan only]: Maximum Concentration (Cmax) of Tislelizumab		From first dose of study treatment up to 4 years, approximately.
Primary	Safety Run-In Substudy[Japan only]: Trough Serum Concentration (Cmin) of tislelizumab		From first dose of study treatment up to 4 years, approximately.
Primary	Safety Run-In Substudy[Japan only]: Area Under the Curve (AUC) of tislelizumab		From first dose of study treatment up to 4 years, approximately.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Secondary	Objective Response Rate (ORR)		From date of randomization up to 4 years, approximately
Secondary	Progression-free survival (PFS)		From date of randomization up to 4 years, approximately
Secondary	Duration of Response (DOR)		From first determination of an objective response up to 4 years, approximately
Secondary	Time to Progression (TTP)		From date of randomization up to 4 years, approximately.
Secondary	Health-Related Quality of Life (HRQoL)		From date of enrollment up to 4 years, approximately.
Secondary	Disease Control Rate (DCR)		From first dose of study treatment up to 4 years, approximately
Secondary	Clinical Benefit Rate (CBR)		From first dose of study treatment up to 4 years, approximately
Secondary	Percentage of participants with adverse events		From date of screening up to 4 years, approximately.
Secondary	Safety Run-In Substudy[Japan only]: Objective Response Rate (ORR)		From date of randomization up to 4 years, approximately.
Secondary	Safety Run-In Substudy[Japan only]: Progression-free survival (PFS)		From date of randomization up 4 years, approximately
Secondary	Safety Run-In Substudy[Japan only]: Duration of Response (DOR)		From date of randomization up 4 years, approximately
Secondary	Safety Run-In Substudy[Japan only]: Overall Survival (OS)		From date of randomization up 4 years, approximately
Secondary	Safety Run-In Substudy[Japan only]: Anti-tislelizumab antibody		From first dose of study treatment up 4 years, approximately
Secondary	Percentage of Participants With Clinically Significant Changes in Vital Signs Findings		From date of enrollment up to 4 years, approximately
Secondary	Percentage of Participants With Clinically Significant Changes in Physical Examination Findings		From date of enrollment up to 4 years, approximately
Secondary	Percentage of Participants With Clinically Significant Changes in Clinical Laboratory Results Findings		From date of enrollment up to 4 years, approximately
Secondary	Percentage of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings		From date of enrollment up to 4 years, approximately