NCT03016312已完成3 期
A Phase III, Multicenter, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) in Combination With Enzalutamide Versus Enzalutamide Alone in Patients With Metastatic Castration-Resistant Prostate Cancer After Failure of an Androgen Synthesis Inhibitor and Failure of, Ineligibility for, or Refusal of a Taxane Regimen
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 759
- 试验地点
- 158
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
This Phase III, multicenter, randomized, open-label study will evaluate the safety and efficacy of atezolizumab (anti-programmed death-ligand 1 [anti-PD-L1] antibody) in combination with enzalutamide compared with enzalutamide alone in participants with mCRPC after failure of an androgen synthesis inhibitor (e.g., abiraterone) and failure of, ineligibility for, or refusal of a taxane regimen. Participants will be randomized to one of the two treatment arms (atezolizumab in combination with enzalutamide, and enzalutamide alone) in a 1:1 ratio (experimental to control arm) in global randomized phase. Participants will receive treatment until investigator-assessed confirmed radiographic disease progression per Prostate Cancer Working Group 3 (PCWG3) criteria or unacceptable toxicity.
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
- Male
- 接受健康志愿者
- 否
入选标准
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Life expectancy greater than or equal to (>/=) 3 months
- •Histologically confirmed adenocarcinoma of the prostate
- •Known castrate-resistant disease with serum testosterone level less than or equal to (</=) 50 nanograms per deciliter (ng/dL) with prior surgical castration or ongoing androgen deprivation for the duration of the study
- •Progressive disease prior to screening by PSA or imaging per PCWG3 criteria during or following the direct prior line of therapy in the setting of medical or surgical castration
- •One prior regimen/line of a taxane-containing regimen for mCRPC or refusal or ineligibility of a taxane-containing regimen
- •Progression on a prior regimen/line of an androgen synthesis inhibitor for prostate cancer
- •Availability of a representative tumor specimen from a site not previously irradiated that is suitable for determination of programmed death-ligand 1 (PD-L1) status via central testing
- •Adequate hematologic and end organ function
排除标准
- •Prior treatment with enzalutamide or any other newer hormonal androgen receptor inhibitor (e.g., apalutamide, ODM-201)
- •Treatment with any approved anti-cancer therapy, including chemotherapy, immunotherapy, radiopharmaceutical or hormonal therapy (with the exception of abiraterone), within 4 weeks prior to initiation of study treatment
- •Treatment with abiraterone within 2 weeks prior to study treatment
- •Structurally unstable bone lesions suggesting impending fracture
- •Known or suspected brain metastasis or active leptomeningeal disease
- •Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during the course of the study
- •Active or history of autoimmune disease or immune deficiency
- •Prior allogeneic stem cell or solid organ transplantation
- •History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
- •Positive human immunodeficiency virus (HIV) test, active tuberculosis, active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
- •Prior treatment with cluster of differentiation (CD)137 agonists or immune checkpoint blockade therapies, including anti Cytotoxic T Lymphocyte-Associated 4 (CTLA4), anti-programmed death 1 (PD-1), and anti-PD-L1 therapeutic antibodies
- •Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug, whichever is shorter, prior to initiation of study treatment
- •Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study
- •History of seizure or any condition that may predispose to seizure within 12 months prior to study treatment, including history of unexplained loss of consciousness or transient ischemic attack
研究组 & 干预措施
Atezolizumab + Enzalutamide
Experimental
Participants will receive atezolizumab along with enzalutamide until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).
干预措施: Atezolizumab (Drug)
Atezolizumab + Enzalutamide
Experimental
Participants will receive atezolizumab along with enzalutamide until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).
干预措施: Enzalutamide (Drug)
Enzalutamide
Active Comparator
Participants will receive enzalutamide alone until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).
干预措施: Enzalutamide (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: Baseline until death from any cause (up to approximately 42 months)
Overall Survival is defined as the time from randomization to death from any cause.
次要结局
- Time to PSA Progression, Assessed as Per PCWG3 Criteria(Baseline until disease progression (up to approximately 42 months))
- Percentage of Participant With Objective Response, as Determined by the Investigator Through Use of PCWG3 Criteria(Baseline until disease progression or death from any cause (up to approximately 42 months))
- Percentage of Participants With Adverse Events(Baseline up to end of study (up to approximately 42 month))
- Plasma Concentration of Enzalutamide(Predose (0 hr) and 1 hr postdose on Day 1 Cycle 1 and 3 (Cycle length: 21 days); pre-dose (within 1 hr) on Day 1 Cycle 8)
- Radiographic Progression-Free Survival (rPFS), as Assessed by the Investigator and Adapted From the PCWG3 Criteria(Baseline until disease progression or death from any cause (up to approximately 42 months))
- Percentage of Participants Who Are Radiographic Progression-Free, as Assessed by the Investigator and Adapted From the PCWG3 Criteria(Months 6, 12)
- Minimum Observed Serum Concentration (Cmin) of Atezolizumab(Pre-infusion (0 hour[hr]) on Day 1 Cycles 1, 2, 3, 4, 8, 12, 16 (Cycle length: 21 days); treatment discontinuation visit, 120 days after last dose (up to approximately 42 months))
- Plasma Concentration of N-Desmethyl Enzalutamide(Predose (0 hr) and 1 hr postdose on Day 1 Cycle 1 and 3 (Cycle length: 21 days); pre-dose (within 1 hr) on Day 1 Cycle 8)
- Percentage of Participants Who Survived at Month 6 and 12(Months 6, 12)
- Time to First Symptomatic Skeletal Event (SSE)(Baseline up to end of study (up to approximately 42 months))
- Percentage of Participants With Greater Than (>) 50 Percent (%) Decrease in Prostate-Specific Antigen (PSA) From Baseline(Baseline until disease progression (up to approximately 42 months))
- Maximum Observed Serum Concentration (Cmax) of Atezolizumab(Day Cycle 1 Day 1 0.5 hr post-infusion (infusion duration: 60 minutes [min]))
- Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab(Predose (0 hr) on Day 1 Cycles 1, 2, 3, 4, 8, 12, 16 (Cycle length: 21 days); at atezolizumab discontinuation visit (30 days after last dose); 120 days after last dose of atezolizumab; up to 42 months)
研究者
研究点 (158)
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