Clinical trial NCT03419897: Study of BGB-A317 in Participants With Previously Treated Unresectable HCC
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatocellular Carcinoma (HCC)
Keywords: Advanced liver cancer
RATIONALE-208
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2018-02-05
Enrollment: 249
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate (ORR) Assessed by Independent Review Committee (IRC)
timeFrame: 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 outcomes:
measure: ORR Assessed by Investigator
timeFrame: From date of first dose to end of study (up to approximately 4 years and 3 months)
measure: Duration of Response (DOR) Assessed by IRC
timeFrame: From date of first dose to end of study (up to approximately 4 years and 3 months)
measure: DOR Event-Free Rate Assessed by IRC
timeFrame: From date of first dose to end of study (up to approximately 4 years and 3 months); Months 12 and 24 reported
measure: DOR Assessed by Investigator
timeFrame: From date of first dose to end of study (up to approximately 4 years and 3 months)
measure: DOR Event-Free Rate Assessed by Investigator
timeFrame: From date of first dose to end of study (up to approximately 4 years and 3 months); Months 12 and 24 reported
measure: Progression-free Survival (PFS) Assessed by IRC
timeFrame: From date of first dose to end of study (up to approximately 4 years and 3 months)
measure: PFS Assessed by Investigator
timeFrame: From date of first dose to end of study (up to approximately 4 years and 3 months)
measure: Overall Survival (OS)
timeFrame: From date of first dose to end of study (up to approximately 4 years and 3 months)
measure: Disease Control Rate (DCR) Assessed by IRC
timeFrame: From date of first dose to end of study (up to approximately 4 years and 3 months)
measure: DCR Assessed by Investigator
timeFrame: From date of first dose to end of study (up to approximately 4 years and 3 months)
measure: Clinical Benefit Rate (CBR) Assessed by IRC
timeFrame: From date of first dose to end of study (up to approximately 4 years and 3 months)
measure: CBR Assessed by Investigator
timeFrame: From date of first dose to end of study (up to approximately 4 years and 3 months)
measure: European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L) Visual Analogue Score (VAS)
timeFrame: Baseline to Cycle 6 Day 1 and Cycle 12 Day 1 (each cycle is 21 days)
measure: European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status
timeFrame: Baseline to Cycle 6 Day 1 and Cycle 12 Day 1 (each cycle is 21 days)
measure: EORTC QLQ - Hepatocellular Carcinoma 18 Questions (HCC18): Index Scores
timeFrame: Baseline to Cycle 6 Day 1 and Cycle 12 Day 1 (each cycle is 21 days)
measure: Number of Participants With Adverse Events
timeFrame: From first dose up to 30 days after the last dose of study drug; up to approximately 4 years and 3 months
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Military Hospital of China
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Chinese Pla General Hospital
state: Beijing
city: Guangzhou
country: China
facility: Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South)
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangdong
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Guangdong
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University Branch Donghu
state: Jiangxi
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Weifang
country: China
facility: Weifang Peoples Hospital
state: Shandong
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Shanghai
country: China
facility: Affiliated Zhongshan Hospital of Fudan University
state: Shanghai
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang University College of Medicine Second Affiliated Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Clichy
country: France
facility: Hopital Beaujon
city: Lyon
country: France
facility: Hopital de La Croix Rousse
city: Montpellier Cedex
country: France
facility: Chu Montpellier Hopital Saint Eloi
city: Nantes Cedex
country: France
facility: Centre Hospitalier Universitaire Nantes Hotel Dieu
city: Nice
country: France
facility: Hopital Larchet Chu Nice
city: Pessac Cedex
country: France
facility: Groupe Hospitalier Du Haut Leveque
city: Poitiers
country: France
facility: Chu de Poitiers Site de La Mileterie
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Essen
country: Germany
facility: Kliniken Essen Mitte Evang Huyssens Stiftung
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg Eppendorf
city: Mainz
country: Germany
facility: Klinikum Johannes Gutenberg Universitaet Mainz
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii Im Marii Skodowskiej Curie Pastwowy Instytut Badawczy
city: Barcelona
country: Spain
facility: Hospital Universitario Vall Dhebron
city: Barcelona
country: Spain
facility: Ico Lhospitalet Hospital Duran I Reynals
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Hm Madrid Sanchinarro
city: Kaohsiung
country: Taiwan
facility: E Da Hospital Kaohsiung
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Greater Manchester
country: United Kingdom
facility: The Christie Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital London Nhs Trust
city: London
country: United Kingdom
facility: Kings College
city: NewCastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
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.