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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 684
- 试验地点
- 122
- 主要终点
- Safety Run-in Sub-study: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
This Phase 3 study was a global, multicenter trial that randomly assigned participants to either tislelizumab or sorafenib as a first-line treatment for adults with advanced liver cancer (hepatocellular carcinoma) that could not be surgically removed. Before enrolling Japanese participants in the main Phase 3 study, a preliminary assessment of safety and tolerability (the Safety Run-In Sub-study) was conducted in Japan.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diagnosis of HCC
- •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
- •No prior systemic therapy for HCC (with the exception of HCC participants enrolled in the safety run-in substudy [Japan only])
- •Measurable disease
- •Child-Pugh score A
- •Easter Cooperative Oncology Group (ECOG) Performance Status ≤ 1
- •Adequate organ function
- •Main Study Key
排除标准
- •Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC histology
- •Tumor thrombus involving main trunk of portal vein or inferior vena cava
- •Loco-regional therapy to the liver within 28 days before randomization
- •Clinical evidence of portal hypertension with bleeding esophageal or gastric varices at Screening, or within 6 months before randomization
- •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
- •Presence at Screening of active immune deficiency or autoimmune disease and/or prior history of any immune deficiency or autoimmune disease 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 randomization
- •History of interstitial lung disease or non-infectious pneumonitis, unless induced by radiation therapy
- •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.
研究组 & 干预措施
Safety Run-In Sub-study
Japanese participants received 200 mg intravenous tislelizumab every 3 weeks to assess preliminary safety and tolerability.
干预措施: Tislelizumab (Drug)
Arm A: Tislelizumab
Participants received 200 mg of intravenous tislelizumab every 3 weeks until intolerable toxicity, withdrawal of consent, or the investigator determined no further benefit from the therapy.
干预措施: Tislelizumab (Drug)
Arm B: Sorafenib
Participants received 400 mg of oral sorafenib twice daily until intolerable toxicity, consent withdrawal, or the investigator deemed no further benefit.
干预措施: Sorafenib (Drug)
结局指标
主要结局
Safety Run-in Sub-study: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
时间窗: From the first dose to 30 days after the last dose, new anticancer therapy, or the analysis cutoff of December 14th, 2023 (a maximum of 64 months)
An adverse event (AE) is any unfavorable or unintended sign (e.g., abnormal lab result), symptom, or disease temporally associated with study drug use, regardless of causality. A serious adverse event (SAE) is defined as any adverse event that: * Resulted in death * Was life-threatening * Required or prolonged hospitalization * Caused disability/incapacity * Lead to a congenital anomaly/birth defect * Was deemed medically significant by the investigator (e.g., required intervention to prevent severe outcomes).
Safety Run-in Sub-study: Serum Concentration of Tislelizumab
时间窗: Cycle 1 and Cycle 5 at end of infusion, 24 hand 72 hours post-dose, and 8 days and 15 days post-dose (each cycle was 3 weeks).
Serum concentration of tislelizumab was a pre-specified primary endpoint for the sub-study only.
Main Study: Overall Survival (OS)
时间窗: Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months)
Defined as the time from the date of randomization to the date of death due to any cause. Median OS was estimated using Kaplan-Meier methodology. Overall survival was a pre-specified primary endpoint for the main study only.
次要结局
- Overall Response Rate (ORR) as Assessed by Blinded Independent Review Committee (BIRC)(Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months))
- Overall Response Rate (ORR) as Assessed by the Investigator(Through the study completion data cut-off date of December 14th, 2023 (up to approximately 65 months))
- Progression Free Survival (PFS) as Assessed by BIRC(Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months))
- Progression Free Survival (PFS) Assessed by the Investigator(Through the study completion data cut-off date of December 14th, 2023 (up to approximately 65 months))
- Duration of Response (DOR) as Assessed by BIRC(Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months))
- Duration of Response (DOR) Assessed by the Investigator(Through the study completion data cut-off date of December 14th, 2023 (up to approximately 65 months))
- Time to Progression (TTP) Assessed by BIRC(Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months))
- Time to Progression (TTP) as Assessed by the Investigator(Through the study completion data cut-off date of December 14th, 2023 (up to approximately 65 months))
- Safety Run-in Sub-study: Overall Survival(Up a to 64 months)
- Disease Control Rate (DCR) as Assessed by BIRC(Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months))
- Disease Control Rate (DCR) as Assessed by the Investigator(Through the study completion data cut-off date of December 14th, 2023 (up to approximately 65 months))
- Clinical Benefit Rate (CBR) as Assessed by BIRC(Through the primary analysis data cut-off date of July 11th, 2022 (up to approximately 55 months))
- Clinical Benefit Rate (CBR) as Assessed by the Investigator(Through the study completion data cut-off date of December 14th, 2023 (up to approximately 65 months))
- Change From Baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Hepatocellular Carcinoma 18 Questions (EORTC QLQ HCC 18) Index Score at Cycle 4(Baseline to Cycle 4 (each cycle was 21 days))
- Change From Baseline in the European EORTC QLQ HCC 18 Index Score at Cycle 6(Baseline to Cycle 6 (Each cycle was 21 days))
- Change From Baseline in the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life Score at Cycle 4(Baseline to Cycle 4 (each cycle was 21 days))
- Change From Baseline in the EQ-5D-5L VAS at Cycle 6(Baseline to Cycle 6 (each cycle was 21 days))
- Change From Baseline in the EORTC QLQ-C30 Global Health Status/Quality of Life Score at Cycle 6(Baseline to Cycle 6 (each cycle was 21 days))
- Change From Baseline in the European Quality of Life 5 Dimensions, 5-level (EQ-5D-5L) Visual Analogue Scale (VAS) at Cycle 4(Baseline to Cycle 4 (each cycle was 21 days))
- Main Study: Number of Participants With Treatment-emergent Adverse Events(From the first dose to 30 days after the last dose, new anticancer therapy, or the study completion analysis cutoff on December 14th, 2023 (a maximum of 61 months for participants in Arm A and 63 months for participants in Arm B).)
- Safety Run-in Sub-study: Number of Participants Who Developed Anti-tislelizumab Antibodies(From the first dose to 30 days after the last dose, new anticancer therapy, or the analysis cutoff of December 14th, 2023 (a maximum of 64 months))