Study of BGB-A317 in Participants With Previously Treated Unresectable HCC

A Phase 2, Open-label, Multicenter Study to Investigate the Efficacy, Safety, and Pharmacokinetics of the Anti-PD-1 Monoclonal Antibody BGB-A317 in Patients With Previously Treated Hepatocellular Unresectable Carcinoma

This study investigated the efficacy, safety, and pharmacokinetics of the anti-PD-1 monoclonal antibody BGB-A317 in participants with previously treated hepatocellular unresectable carcinoma.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 249
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230601
      • The Second Hospital of Anhui Medical University
    • Hefei, Anhui, China, 230000
      • Anhui Provincial Hospital
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer hospital
    • Beijing, Beijing, China, 100853
      • Chinese PLA General Hospital
    • Beijing, Beijing, China, 100039
      • Military Hospital of China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital of Southern Medical University
    • Guangzhou, Guangdong, China, 510245
      • Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South)
    • Shenzhen, Guangdong, China, 518036
      • Peking University Shenzhen Hospital
  • 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
  • Jiangsu
    • Xuzhou, Jiangsu, China, 221000
      • Xuzhou Central Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The Second Affiliated Hospital of Nanchang University
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of Nanchang University Branch Donghu
  • Jilin
    • Changchun, Jilin, China, 130021
      • Jilin Cancer Hospital
  • Shandong
    • Weifang, Shandong, China, 261000
      • Weifang Peoples Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Fudan University Shanghai Cancer Center
    • Shanghai, Shanghai, China, 200032
      • Affiliated Zhongshan Hospital of Fudan University
  • Tianjin
    • Tianjin, Tianjin, 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
    • Hangzhou, Zhejiang, China, 310009
      • Zhejiang University College of Medicine Second Affiliated Hospital
    • Wenzhou, Zhejiang, China, 325000
      • The First Affiliated Hospital of Wenzhou Medical University
• France
  • Clichy, France, 92210
    • Hôpital Beaujon
  • Lyon, France, 69317
    • Hopital de la croix rousse
  • Montpellier Cedex, France, 34295
    • Chu Montpellier Hopital Saint Eloi
  • Nantes Cedex, France, 44093
    • Centre Hospitalier Universitaire Nantes Hotel Dieu
  • Nice, France, 6200
    • Hopital Larchet Chu Nice
  • Pessac Cedex, France, 33604
    • Groupe Hospitalier Du Haut Leveque
  • Poitiers, France, 86000
    • Chu de Poitiers Site de La Mileterie
  • Rennes, France, 35043
    • Centre Eugène Marquis
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Germany
  • Essen, Germany, 45136
    • Kliniken Essen Mitte Evang Huyssens Stiftung
  • Hamburg, Germany, 20251
    • Universitatsklinikum Hamburg Eppendorf
  • Mainz, Germany, 55131
    • Klinikum Johannes Gutenberg Universitaet Mainz
• Italy
  • Pisa, Italy, 56126
    • Azienda Ospedaliero Universitaria Pisana
  • Rozzano, Italy, 20089
    • Istituto Clinico Humanitas
• Poland
  • Warszawa, Poland, 02-034
    • Narodowy Instytut Onkologii Im Marii Skodowskiej Curie Pastwowy Instytut Badawczy
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall dHebron
  • Barcelona, Spain, 08908
    • Ico Lhospitalet Hospital Duran I Reynals
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28050
    • Hospital Universitario Hm Madrid Sanchinarro
• Taiwan
  • Kaohsiung, Taiwan, 82445
    • E Da Hospital Kaohsiung
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 10048
    • National Taiwan University Hospital
  • Taoyuan, 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
  • NewCastle Upon Tyne, United Kingdom, NE7 7DN
    • Freeman Hospital

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

1. Histologically confirmed HCC
2. Participants with Barcelona Clinic Liver Cancer (BCLC) Stage C, or BCLC stage B not amenable to locoregional therapy or relapsed after locoregional therapy, and not amenable to a curative treatment approach
3. Has received at least 1 line of systemic therapy for unresectable HCC
4. Has at least 1 measurable lesion as defined per RECIST v1.1
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. Prior therapies targeting PD-1 or PD-L1
3. Has known brain or leptomeningeal metastasis
4. Tumor thrombus involving main trunk of portal vein or inferior vena cava
5. Loco-regional therapy to the liver within 4 weeks before enrollment
6. Medical history of interstitial lung disease, non-infectious pneumonitis or uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, or acute lung diseases

7. Has received:

   1. Within 28 days or 5 half-lives (whichever is shorter) of the first study drug administration: any chemotherapy, immunotherapy (eg, interleukin, interferon, thymoxin) or any investigational therapies
   2. Within 14 days of the first study drug administration: sorafenib, regorafenib, or any Chinese herbal medicine or Chinese patent medicines used to control cancer
8. Active autoimmune diseases or history of autoimmune diseases that may relapse
9. 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 study drug administration

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tislelizumab; 200 milligrams once every 3 weeks	Drug: Tislelizumab; Administered intravenously; Other Names: BGB-A317

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Assessed by Independent Review Committee (IRC)	ORR is defined as the percentage of participants with complete response (CR) and partial response (PR) as the best overall response, as determined by an IRC using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR is defined as disappearance of all target lesions and PR is defined as at least a 30% decrease in the sum of diameters of target lesions.	From date of first dose to primary analysis data cut-off date of 30-June-2021 (up to approximately 3 years and 3 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR Assessed by Investigator	ORR is defined as the percentage of participants with CR and PR as the best overall response, as determined by investigator assessment using RECIST v1.1. CR is defined as disappearance of all target lesions and PR is defined as at least a 30% decrease in the sum of diameters of target lesions.	From date of first dose to end of study (up to approximately 4 years and 3 months)
Duration of Response (DOR) Assessed by IRC	DOR is defined as the time from the date that response criteria are first met to the date that progressive disease is objectively documented or death, whichever comes first, as assessed by the IRC using RECIST v1.1	From date of first dose to end of study (up to approximately 4 years and 3 months)
DOR Event-Free Rate Assessed by IRC	DOR is defined as the time from the date that response criteria are first met to the date that progressive disease is objectively documented or death, whichever comes first, as assessed by the IRC using RECIST v1.1. The Kaplan-Meier method was used to estimate the percentage of participants who were event-free for progression or death at 12 and 24 months with 95% confidence intervals estimated using Greenwood's formula.	From date of first dose to end of study (up to approximately 4 years and 3 months); Months 12 and 24 reported
DOR Assessed by Investigator	DOR is defined as the time from the date that response criteria are first met to the date that progressive disease is objectively documented or death, whichever comes first, as assessed by the investigator using RECIST v1.1	From date of first dose to end of study (up to approximately 4 years and 3 months)
DOR Event-Free Rate Assessed by Investigator	DOR is defined as the time from the date that response criteria are first met to the date that progressive disease is objectively documented or death, whichever comes first, as assessed by the investigator using RECIST v1.1. The Kaplan-Meier method was used to estimate the percentage of participants who were event-free for progression or death at 12 and 24 months with 95% confidence intervals estimated using Greenwood's formula.	From date of first dose to end of study (up to approximately 4 years and 3 months); Months 12 and 24 reported
Progression-free Survival (PFS) Assessed by IRC	PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by the IRC using RECIST v1.1	From date of first dose to end of study (up to approximately 4 years and 3 months)
PFS Assessed by Investigator	PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by the investigator using RECIST v1.1	From date of first dose to end of study (up to approximately 4 years and 3 months)
Overall Survival (OS)	OS is defined as the time from first study drug administration to the date of death due to any cause	From date of first dose to end of study (up to approximately 4 years and 3 months)
Disease Control Rate (DCR) Assessed by IRC	DCR is defined as the percentage of participants whose best overall response is CR, PR, or stable disease (SD) as assessed by the IRC using RECIST v1.1	From date of first dose to end of study (up to approximately 4 years and 3 months)
DCR Assessed by Investigator	DCR is defined as the percentage of participants whose best overall response is CR, PR, or stable disease (SD) as assessed by the investigator using RECIST v1.1	From date of first dose to end of study (up to approximately 4 years and 3 months)
Clinical Benefit Rate (CBR) Assessed by IRC	CBR is defined as the percentage of participants who have CR, PR, or SD of ≥ 24 weeks in duration as assessed by the IRC using RECIST v1.1	From date of first dose to end of study (up to approximately 4 years and 3 months)
CBR Assessed by Investigator	CBR is defined as the percentage of participants who have CR, PR, or SD of ≥ 24 weeks in duration as assessed by the investigator using RECIST v1.1	From date of first dose to end of study (up to approximately 4 years and 3 months)
European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L) Visual Analogue Score (VAS)	Mean change from baseline in EQ-5D-5L VAS. The EQ-5D-5L measures health outcomes using a VAS to record a participant's self-rated health on a scale from 0 to 100, where 100 is 'the best health you can imagine' and 0 is 'the worst health you can imagine.' A higher score indicates better health outcomes.	Baseline to Cycle 6 Day 1 and Cycle 12 Day 1 (each cycle is 21 days)
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status	Mean change from baseline in EORTC QLQ-C30 Global Health Status/Quality of Life score. The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of cancer patients. 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.	Baseline to Cycle 6 Day 1 and Cycle 12 Day 1 (each cycle is 21 days)
EORTC QLQ - Hepatocellular Carcinoma 18 Questions (HCC18): Index Scores	Mean change from baseline in EORTC QLQ HCC18 Index Scores. The EORTC QLQ HCC18 is a specific questionnaire module that assesses quality of life of cancer patients 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.	Baseline to Cycle 6 Day 1 and Cycle 12 Day 1 (each cycle is 21 days)
Number of Participants With Adverse Events	Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), which includes laboratory tests, physical exams, electrocardiogram results and vital signs	From first dose up to 30 days after the last dose of study drug; up to approximately 4 years and 3 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Ren Z, Ducreux M, Abou-Alfa GK, Merle P, Fang W, Edeline J, Li Z, Wu L, Assenat E, Hu S, Rimassa L, Zhang T, Blanc JF, Pan H, Ross P, Yen CJ, Tran A, Shao G, Bouattour M, Chen Y, Meyer T, Hou J, Tougeron D, Bai Y, Hou MM, Meng Z, Wu J, Li V, Chica-Duque S, Cheng AL. Tislelizumab in Patients with Previously Treated Advanced Hepatocellular Carcinoma (RATIONALE-208): A Multicenter, Non-Randomized, Open-Label, Phase 2 Trial. Liver Cancer. 2022 Oct 4;12(1):72-84. doi: 10.1159/000527175. eCollection 2023 Feb.
• Serrano D, Podger L, Barnes G, Song J, Tang B. Psychometric validation of the EORTC QLQ-HCC18 in patients with previously treated unresectable hepatocellular carcinoma. Qual Life Res. 2022 Mar;31(3):937-950. doi: 10.1007/s11136-021-02992-1. Epub 2021 Sep 13.

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2018
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): July 6, 2022

Study Registration Dates

• First Submitted: January 29, 2018
• First Submitted That Met QC Criteria: February 1, 2018
• First Posted (Actual): February 5, 2018

Study Record Updates

• Last Update Posted (Actual): October 26, 2024
• Last Update Submitted That Met QC Criteria: October 23, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Advanced liver cancer; RATIONALE-208
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Antineoplastic Agents, Immunological; Antineoplastic Agents; Tislelizumab
• Other Study ID Numbers: BGB-A317-208; 2017-003983-10 (EudraCT Number); CTR20171257 (Registry Identifier: Center for drug evaluation, CFDA)

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