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

Hepatocellular Carcinoma (HCC) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03419897
• Other study ID #: BGB-A317-208
• Secondary ID: 2017-003983-10CT
• Status: Completed
• Phase: Phase 2
• Start date: April 9, 2018
• Est. completion date: July 6, 2022

Study information

• Verified date: July 2023
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 249
• Est. completion date: July 6, 2022
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Hepatocellular Carcinoma (HCC)

Intervention

Drug:
• Tislelizumab
Administered intravenously

Locations

Country	Name	City	State
China	302 Military Hospital of China	Beijing	Beijing
China	Beijing Cancer Hospital	Beijing	Beijing
China	Cancer Hospital Chinese Academy of Medical Sciences	Beijing	Beijing
China	Chinese PLA General Hospital Medical School of Chinese PLA	Beijing
China	Jilin Cancer Hospital	Changchun	Jilin
China	The First Hospital of Jilin University	Changchun	Jilin
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Nanfang Hospital of Southern Medical University	Guangzhou	Guangdong
China	Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University	Guangzhou	Guangdong
China	Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine	Hangzhou	Zhejiang
China	The First Affiliated Hospital, Zhejiang University	Hangzhou	Zhejiang
China	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Anhui Provincial Hospital	Hefei	Anhui
China	The Second Hospital of Anhui Medical Hospital	Hefei	Anhui
China	The First affiliated hospital of Nanchang University	Nanchang	Jiangxi
China	The Second Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Shanghai Cancer Hospital, Fudan University	Shanghai	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai	Shanghai
China	Peking University Shenzhen Hospital	Shenzhen	Guangdong
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin	Tianjin
China	Weifang People's Hospital	Weifang	Shandong
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	Hubei Cancer Hospital	Wuhan	Hubei
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan	Hubei
China	Xuzhou Central Hospital	Xuzhou	Jiangsu
China	Henan Cancer Hospital	Zhengzhou	Henan
France	Hopital Beaujon	Clichy	Paris
France	Centre Hospitalier de la Croix Rousse	Lyon	Rhone
France	Centre Hospitalier de la Croix Rousse	Lyon	Rhone
France	Hopital Saint Eloi	Montpellier	Herault
France	CHU Nice - Hôpital de l'Archet 2	Nice Cedex 3	Alpes Maritimes
France	Groupe Hospitalier Sud - Hôpital Haut Lévêque	Pessac Cedex	Gironde
France	CHU Poitiers - Hôpital la Milétrie	Poitiers Cedex	Vienne
France	CRLCC Eugene Marquis	Rennes cedex	Ille Et Vilaine
France	Institut Gustave Roussy	Villejuif cedex	Val De Marne
Germany	Kliniken Essen-Mitte	Essen	Nordrhein Westfalen
Germany	Universitaetsklinikum Hamburg-Eppendorf	Hamburg
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz	Rheinland Pflaz
Italy	Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)	Bergamo
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Università Campus Bio-Medico di Roma	Roma
Italy	Istituto Clinico Humanitas	Rozzano	Milano
Poland	Centrum Badan Klinicznych Piotr Napora Lekarze Spolka Partnerska	Warszawa
Poland	Centrum Onkologii-Instytut im. M. Sklodowskiej Curie	Wroclaw
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario Reina Sofia	Córdoba
Spain	ICO l'Hospitalet - Hospital Duran i Reynals	L'Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario HM Madrid Sanchinarro	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramón Y Cajal	Madrid
Taiwan	Chiayi Chang Gung Memorial Hospital of the Chang Gung Medical Foundation	Chiayi City
Taiwan	Chang Gung Memorial Hospital, Kaohsiung	Kaohsiung
Taiwan	E-Da Cancer Hospital	Kaohsiung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital, Linkou	Taoyuan
United Kingdom	Queen Elizabeth Hospital	Birmingham	West Midlands
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow	Strathclyde
United Kingdom	King's College Hospital	London	Greater London
United Kingdom	Royal Free Hospital	London	Greater London
United Kingdom	The Christie NHS Foundation Trust	Manchester	England
United Kingdom	Freeman Hospital	Newcastle Upon Tyne

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Countries where clinical trial is conducted

China,  France,  Germany,  Italy,  Poland,  Spain,  Taiwan,  United Kingdom, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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