A Randomized, Open-Label, Phase 3 Study to Investigate the Efficacy and Safety of BGB-B2033 Compared With Investigator Choice of Sorafenib or Lenvatinib in Patients With Hepatocellular Carcinoma That Progressed Upon Prior Systemic Treatment
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 492
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
The goal of this clinical trial is to learn how well BGB-B2033 works and how safe it is in people with hepatocellular carcinoma (HCC) who have previously received up to two treatments that included programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) medicines. Researchers will compare BGB-B2033 with either sorafenib or lenvatinib chosen by the study doctor to see which treatment works better and is safer.
The main questions it aims to answer are:
- Does BGB-B2033 help control or slow the growth of liver cancer?
- What medical problems or side effects do participants have while taking BGB-B2033?
- Does BGB-B2033 help to prolong the survival for liver cancer participants over Lenvatinib/sorafenib?
详细描述
Hepatocellular carcinoma (HCC) is the most common type of liver cancer. It can develop when abnormal cells in the liver grow uncontrollably and may spread to other parts of the body. For people whose cancer has returned or continued to grow after treatment, additional treatment options are needed.
BGB-B2033 is a new investigational drug designed to bind to a protein called glypican-3 (GPC3), a protein found on certain cancer cells and cells of the immune system, helping the immune system to recognize and attack the cancer cells. Lenvatinib and sorafenib are approved medicines that work by blocking signals that help cancer cells grow and form new blood vessels.
The purpose of this study is to test whether BGB-B2033 is safe and can help treat HCC in adults whose cancer has been treated with up to 2 previous treatments that included programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD-L1) medicines. The main goal of the study is to see how well BGB-B2033 controls cancer compared to the treatments selected by the study doctor (either lenvatinib or sorafenib).
This study has 2 treatment groups. Participants will be randomly assigned, like flipping a coin, to receive either:
- BGB-B2033, given by intravenous infusion.
- Sorafenib, taken by mouth or lenvatinib, taken by mouth per their doctor's choice The study will enroll approximately 492 adults with HCC at multiple centers worldwide. Participants will make regular visits to the clinic for treatment, health checks, blood tests, and tumor and imaging tests.
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
- •Participants must have histologically confirmed Hepatocellular Carcinoma (HCC) that is not amenable to curative surgical or locoregional therapies.
- •Participants must have documented disease progression or intolerance after at least 1 but not exceeding 2 prior lines of systemic therapy containing Programmed Cell Death Protein 1 / Programmed Death-Ligand 1 (PD-1/PD-L1). Prior cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) targeting therapy or v ascular endothelial growth factor (VEGF) is permitted but not required.
- •Glypican-3 (GPC3) expression level must be known for stratification.
- •Participants must have at least 1 measurable lesion as assessed by RECIST v1.1
- •Participants must have a stable Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤
排除标准
- •Prior therapy targeting GPC3 or 4-1BB
- •Participants not feasible to be treated with lenvatinib or sorafenib
- •prior exposure to both medications
- •siginificant precautions of administering lenvatinib or sorafenib such as clinically significant active bleeding within 3 months prior to first dose, tumor thombus involving main portal vein trunk, inferior vena cava, or cardiac involvement,
- •any history of gastrointestinal perforation or larger than grade 3 fistula within 6 months prior to the first dose,
- •or any history of heart failure meeting NYHA classification III or IV ≤ 6 months before the first dose of study drug.
- •Active leptomeningeal disease or uncontrolled and untreated brain metastasis
- •History of previous or present encephalopathy
- •Presence of clinically significant ascites ((≥ Grade 2).
- •History of liver transplantation
- •NOTE: Other eligbility criteria may apply.
研究组 & 干预措施
BGB-B2033
Participants are randomized to receive BGB-B2033 until disease progression, unacceptable toxicity, withdrawal of consent, death, or the end of the study, whichever occurs first.
干预措施: BGB-B2033 (Drug)
Investigator's choice: Lenvatinib OR sorafenib
Participants are randomized to receive either lenvatinib or sorafenib, selected by the investigator before treatment, until disease progression, unacceptable toxicity, withdrawal of consent, death, or the end of the study, whichever occurs first.
干预措施: Sorafenib (Drug)
Investigator's choice: Lenvatinib OR sorafenib
Participants are randomized to receive either lenvatinib or sorafenib, selected by the investigator before treatment, until disease progression, unacceptable toxicity, withdrawal of consent, death, or the end of the study, whichever occurs first.
干预措施: Lenvatinib (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: Up to approximately 3.5 years
OS is defined as the time from randomization to the date of death from any cause.
次要结局
- Overall Response Rate (ORR)(Up to approximately 3.5 years)
- Duration of Response (DOR)(Up to approximately 3.5 years)
- Progression Free Survival Rate (PFS)(Up to approximately 3.5 years)
- Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Immune-Related Adverse Events (imAEs)(From first dose until either 30 days after the last dose of study drug(s) or initiation of new anticancer therapy, whichever occurs first (Up to approximately 3.5 years))
- Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Hepatocellular Carcinoma 18-question module [EORTC QLQ-HCC18]) Fatigue Scores(From baseline (Cycle 1 Day 1, predose) through the Safety Follow-up Visit (30 days after last dose) with assessments every 2 cycles through EOT. Each cycle is 21 days.)
- Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Function 17 (EORTC QLQ-F17) Global Health Status (GHS), and Physical/Role Functioning scores(From baseline (Cycle 1 Day 1, predose) through the Safety Follow-up Visit (30 days after last dose) with assessments every 2 cycles through EOT.)
- Time to Deterioration of Fatigue Measured by EORTC QLQ-HCC18(From randomization until the first clinically meaningful deterioration, end of treatment, withdrawal of consent, death, or end of study, as applicable (Up to approximately 3.5 years))
- Time to Deterioration of Global Health Status and Physical/Role Functioning Measured by EORTC QLQ-F17.(From randomization until the first clinically meaningful deterioration, end of treatment, withdrawal of consent, death, or end of study, as applicable ((Up to approximately 3.5 years).)