A Randomized, Controlled Phase 3 Study of Cabozantinib (XL184) in Combination With Atezolizumab Versus Sorafenib in Subjects With Advanced Hepatocellular Carcinoma Who Have Not Received Previous Systemic Anticancer Therapy
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Exelixis
- 入组人数
- 837
- 试验地点
- 245
- 主要终点
- Progression Free Survival (PFS) for the Experimental Arm Versus the Control Arm in the PFS Intent to Treat (PITT) Population
研究概览
简要总结
This Phase 3 study evaluates the safety and efficacy of cabozantinib in combination with atezolizumab versus the standard of care sorafenib in adults with advanced hepatocellular carcinoma (HCC) who have not received previous systemic anticancer therapy. A single-agent cabozantinib arm will be enrolled in which participants receive single agent cabozantinib in order to determine its contribution to the overall safety and efficacy of the combination with atezolizumab.
详细描述
This is a multicenter, randomized, open-label, controlled Phase 3 trial of cabozantinib in combination with atezolizumab versus sorafenib in adults with advanced HCC who have not received previous systemic anticancer therapy in the advanced HCC setting. The primary objective of this study is to evaluate the effect of cabozantinib in combination with atezolizumab on the duration of progression-free survival (PFS) and duration of overall survival (OS) versus sorafenib. The secondary objective is to evaluate the activity of single-agent cabozantinib compared with sorafenib in this patient population.
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
- •Histological or cytological diagnosis of HCC or clinical diagnosis of HCC in cirrhotic patients by Computed Tomography (CT) or Computed Tomography (MRI) per the American Association for the Study of Liver Diseases (AASLD) 2018 or European Association for the Study of the Liver (EASL) 2018 guidelines.
- •The participant has disease that is not amenable to a curative treatment approach (eg, transplant, surgery, ablation therapy) or locoregional therapy (eg, TACE).
- •Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as determined by the Investigator.
- •Barcelona Clinic Liver Cancer (BCLC) stage Category B or C.
- •Child-Pugh Score of A.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
排除标准
- •Known fibrolamellar carcinoma, sarcomatoid HCC or mixed hepatocellular cholangiocarcinoma.
- •Prior systemic anticancer therapy for advanced HCC including but not limited to chemotherapy, small molecule kinase inhibitors, and immune checkpoint inhibitors (ICIs). Participants who have received local intratumoral or arterial chemotherapy are eligible; local anticancer therapy within ≥ 28 days before randomization
- •Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 8 weeks prior to randomization.
- •Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 8 weeks prior to randomization.
- •Concomitant anticoagulation with oral anticoagulants
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Experimental arm
Participants with advanced HCC will receive cabozantinib 40 milligrams (mg) oral, once daily (qd) + atezolizumab 1200 mg infusion, once every 3 weeks (q3w)
干预措施: Cabozantinib (Drug)
Experimental arm
Participants with advanced HCC will receive cabozantinib 40 milligrams (mg) oral, once daily (qd) + atezolizumab 1200 mg infusion, once every 3 weeks (q3w)
干预措施: Atezolizumab (Drug)
Control arm
Participants with advanced HCC will receive sorafenib 400 mg twice a day (bid)
干预措施: Sorafenib (Drug)
Single-Agent Cabozantinib arm
Participants with advanced HCC will receive cabozantinib 60 mg qd
干预措施: Cabozantinib (Drug)
结局指标
主要结局
Progression Free Survival (PFS) for the Experimental Arm Versus the Control Arm in the PFS Intent to Treat (PITT) Population
时间窗: From the date of first participant randomization up to 28 months
PFS was defined as the time from randomization to the earlier of either the date of radiographic progression defined as a 20% increase in the sum of the longest diameters of target lesions, or the unequivocal appearance of new lesions, or progression of non-target disease per Blinded Independent Radiology Committee (BIRC) or the date of death due to any cause per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Overall Survival (OS) for the Experimental Arm Versus the Control Arm in the ITT Population
时间窗: From the date of first participant randomization up to 36 months
OS was defined as the time from randomization to death due to any cause.
次要结局
- PFS for the Single-Agent Cabozantinib Arm Versus the Control Arm in the ITT Population(From the date of first participant randomization up to 28 months)