A Phase III, Open-Label, Randomized Study of Atezolizumab With Lenvatinib or Sorafenib Versus Lenvatinib or Sorafenib Alone in Hepatocellular Carcinoma Previously Treated With Atezolizumab and Bevacizumab
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 557
- 试验地点
- 234
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
This is a Phase III, open-label, multicenter, randomized, two-arm study designed to evaluate the efficacy and safety of atezolizumab plus either lenvatinib or sorafenib versus lenvatinib or sorafenib alone in participants with locally advanced or metastatic Hepatocellular Carcinoma (HCC) who have progressed on prior systemic treatment with atezolizumab plus bevacizumab combination.
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
- •Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology/ cytology or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic patients.
- •Disease progression following prior atezolizumab plus bevacizumab combination treatment for HCC, for at least 4 consecutive treatment cycles, and 2 subsequent tumor assessments. It is required that at least 1 tumor assessment shows either stable disease (SD), partial response (PR), or complete response (CR).
- •At least one measurable (per RECIST v1.1) target lesion that has not been previously treated with local therapy or, if the target lesion is within the field of previous local therapy, has subsequently progressed in accordance with RECIST v1.
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 within 7 days prior to randomization
- •Child-Pugh class A within 7 days prior to randomization
- •Adequate hematologic and end-organ function
排除标准
- •Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.
- •History of leptomeningeal disease
- •History of hepatic encephalopathy, preceding 6 months, unresponsive to therapy within 3 days
- •Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
- •History of malignancy other than HCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
研究组 & 干预措施
Lenvatinib or Sorafenib
Participants will receive lenvatinib or sorafenib. Treatment will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
干预措施: Sorafenib (Drug)
Atezolizumab + Lenvatinib or Sorafenib
Participants will receive atezolizumab plus lenvatinib or sorafenib. Treatment will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
干预措施: Atezolizumab (Drug)
Atezolizumab + Lenvatinib or Sorafenib
Participants will receive atezolizumab plus lenvatinib or sorafenib. Treatment will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
干预措施: Lenvatinib (Drug)
Atezolizumab + Lenvatinib or Sorafenib
Participants will receive atezolizumab plus lenvatinib or sorafenib. Treatment will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
干预措施: Sorafenib (Drug)
Lenvatinib or Sorafenib
Participants will receive lenvatinib or sorafenib. Treatment will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
干预措施: Lenvatinib (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: Randomization until death from any cause (approximately 42 months)
Overall survival (OS) is defined as the time from randomization into the study to death from any cause.
次要结局
- Percentage of Participants With Adverse Events(Throughout study duration (approximately 42 months))
- Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab(Throughout study (approximately 42 months))
- Progression Free Survival (PFS)(Randomization until the first occurrence of disease progression or death from any cause whichever occurs first (approximately 42 months))
- Confirmed Objective Response Rate (ORR)(Approximately 42 months)
- Time to Progression (TTP)(Randomization until the first occurrence of disease progression (approximately 42 months))
- Duration of Response (DOR)(Time from the first occurrence of a confirmed documented objective response to disease progression or death from any cause whichever occurs first (approximately 42 months))
- Time to confirmed deterioration (TTCD)(Randomization to first deterioration maintained for two consecutive assessments, or one assessment followed by death from any cause wthin 3 weeks or 6 weeks (approximately 42 months))
- Serum Concentration of Atezolizumab(At pre-defined intervals from first administration of study drug to approximately 42 months)
- Percentage of Participants With Adverse Events for Combination Treatment, Adverse Events Related to Atezolizumab, and TKI-Related Adverse Events(Throughtout study (approximately 42 months))