Study of BGB-A317 in Participants With Previously Treated Unresectable HCC
- Registration Number
- NCT03419897
- Lead Sponsor
- BeiGene
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 249
- Histologically confirmed HCC
- 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
- Has received at least 1 line of systemic therapy for unresectable HCC
- Has at least 1 measurable lesion as defined per RECIST v1.1
- Child-Pugh score A
- Easter Cooperative Oncology Group (ECOG) Performance Status ≤ 1
- Adequate organ function
Key
-
Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC histology
-
Prior therapies targeting PD-1 or PD-L1
-
Has known brain or leptomeningeal metastasis
-
Tumor thrombus involving main trunk of portal vein or inferior vena cava
-
Loco-regional therapy to the liver within 4 weeks before enrollment
-
Medical history of interstitial lung disease, non-infectious pneumonitis or uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, or acute lung diseases
-
Has received:
- 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
- Within 14 days of the first study drug administration: sorafenib, regorafenib, or any Chinese herbal medicine or Chinese patent medicines used to control cancer
-
Active autoimmune diseases or history of autoimmune diseases 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 study drug administration
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Tislelizumab Tislelizumab 200 milligrams once every 3 weeks
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) Assessed by Independent Review Committee (IRC) From date of first dose to primary analysis data cut-off date of 30-June-2021 (up to approximately 3 years and 3 months) 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.
- Secondary Outcome Measures
Name Time Method Progression-free Survival (PFS) Assessed by IRC From date of first dose to end of study (up to approximately 4 years and 3 months) 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
PFS Assessed by Investigator From date of first dose to end of study (up to approximately 4 years and 3 months) 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
DCR Assessed by Investigator From date of first dose to end of study (up to approximately 4 years and 3 months) 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
Duration of Response (DOR) Assessed by IRC From date of first dose to end of study (up to approximately 4 years and 3 months) 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
DOR Event-Free Rate Assessed by Investigator From date of first dose to end of study (up to approximately 4 years and 3 months); Months 12 and 24 reported 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.
EORTC QLQ - Hepatocellular Carcinoma 18 Questions (HCC18): Index Scores Baseline to Cycle 6 Day 1 and Cycle 12 Day 1 (each cycle is 21 days) 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.
ORR Assessed by Investigator From date of first dose to end of study (up to approximately 4 years and 3 months) 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.
DOR Assessed by Investigator From date of first dose to end of study (up to approximately 4 years and 3 months) 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
Clinical Benefit Rate (CBR) Assessed by IRC From date of first dose to end of study (up to approximately 4 years and 3 months) 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
CBR Assessed by Investigator From date of first dose to end of study (up to approximately 4 years and 3 months) 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
European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L) Visual Analogue Score (VAS) Baseline to Cycle 6 Day 1 and Cycle 12 Day 1 (each cycle is 21 days) 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.
Overall Survival (OS) From date of first dose to end of study (up to approximately 4 years and 3 months) OS is defined as the time from first study drug administration to the date of death due to any cause
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status Baseline to Cycle 6 Day 1 and Cycle 12 Day 1 (each cycle is 21 days) 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.
DOR Event-Free Rate Assessed by IRC From date of first dose to end of study (up to approximately 4 years and 3 months); Months 12 and 24 reported 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.
Disease Control Rate (DCR) Assessed by IRC From date of first dose to end of study (up to approximately 4 years and 3 months) 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
Number of Participants With Adverse Events From first dose up to 30 days after the last dose of study drug; up to approximately 4 years and 3 months 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
Trial Locations
- Locations (54)
The Second Hospital of Anhui Medical University
🇨🇳Hefei, Anhui, China
Military Hospital of China
🇨🇳Beijing, Beijing, China
Chinese Pla General Hospital
🇨🇳Beijing, Beijing, China
Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South)
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospital of Nanchang University Branch Donghu
🇨🇳Nanchang, Jiangxi, China
Weifang Peoples Hospital
🇨🇳Weifang, Shandong, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, Shanghai, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Hubei Cancer Hospital
🇨🇳Wuhan, Hubei, China
Xuzhou Central Hospital
🇨🇳Xuzhou, Jiangsu, China
The Second Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
Jilin Cancer Hospital
🇨🇳Changchun, Jilin, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China
The Christie Hospital
🇬🇧Greater Manchester, United Kingdom
Royal Free Hospital London Nhs Trust
🇬🇧London, United Kingdom
Kings College
🇬🇧London, United Kingdom
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
Nanfang Hospital of Southern Medical University
🇨🇳Guangzhou, Guangdong, China
Anhui Provincial Hospital
🇨🇳Hefei, Anhui, China
Peking University Shenzhen Hospital
🇨🇳Shenzhen, Guangdong, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, Heilongjiang, China
Affiliated Zhongshan Hospital of Fudan University
🇨🇳Shanghai, Shanghai, China
Tianjin Medical University Cancer Institute and Hospital
🇨🇳Tianjin, Tianjin, China
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
The First Affiliated Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Zhejiang University College of Medicine Second Affiliated Hospital
🇨🇳Hangzhou, Zhejiang, China
Hopital de La Croix Rousse
🇫🇷Lyon, France
Chu Montpellier Hopital Saint Eloi
🇫🇷Montpellier Cedex, France
Centre Hospitalier Universitaire Nantes Hotel Dieu
🇫🇷Nantes Cedex, France
Hopital Larchet Chu Nice
🇫🇷Nice, France
Groupe Hospitalier Du Haut Leveque
🇫🇷Pessac Cedex, France
Chu de Poitiers Site de La Mileterie
🇫🇷Poitiers, France
Centre Eugene Marquis
🇫🇷Rennes, France
Kliniken Essen Mitte Evang Huyssens Stiftung
🇩🇪Essen, Germany
Universitatsklinikum Hamburg Eppendorf
🇩🇪Hamburg, Germany
Klinikum Johannes Gutenberg Universitaet Mainz
🇩🇪Mainz, Germany
Narodowy Instytut Onkologii Im Marii Skodowskiej Curie Pastwowy Instytut Badawczy
🇵🇱Warszawa, Poland
Hospital Universitario Vall Dhebron
🇪🇸Barcelona, Spain
Hospital Universitario Hm Madrid Sanchinarro
🇪🇸Madrid, Spain
E Da Hospital Kaohsiung
🇨🇳Kaohsiung, Taiwan
Ico Lhospitalet Hospital Duran I Reynals
🇪🇸Barcelona, Spain
Linkou Chang Gung Memorial Hospital
🇨🇳Taoyuan, Taiwan
The First Affiliated Hospital of Wenzhou Medical University
🇨🇳Wenzhou, Zhejiang, China
Institut Gustave Roussy
🇫🇷Villejuif, France
Hopital Beaujon
🇫🇷Clichy, France
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Italy
Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
Hospital Universitario La Paz
🇪🇸Madrid, Spain
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Queen Elizabeth Hospital
🇬🇧Birmingham, United Kingdom
Freeman Hospital
🇬🇧NewCastle Upon Tyne, United Kingdom