A Phase III, Multicenter, Randomized, Placebo-Controlled Study of Atezolizumab (Anti-PD-L1 Antibody) in Combination With Nab-Paclitaxel Compared With Placebo With Nab-Paclitaxel for Patients With Previously Untreated Metastatic Triple-Negative Breast Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 902
- 试验地点
- 247
- 主要终点
- OS in Participants With Detectable PD-L1
研究概览
简要总结
This multicenter, randomized, double-blind study evaluated the efficacy, safety, and pharmacokinetics of atezolizumab (MPDL3280A) administered with nab-paclitaxel compared with placebo in combination with nab-paclitaxel in participants with locally advanced or metastatic triple-negative breast cancer (TNBC) who have not received prior systemic therapy for metastatic breast cancer (mBC). The safety of single-agent nab-paclitaxel has been determined in previous studies of participants with mBC and the safety data to date suggest that atezolizumab can be safely combined with standard chemotherapy agents.
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
- Double (Participant, Investigator)
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
- •Metastatic or locally advanced, histologically documented TNBC characterized by absence of human epidermal growth factor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) expression
- •No prior chemotherapy or targeted systemic therapy for inoperable locally advanced or metastatic TNBC
- •Eligible for taxane monotherapy (i.e., absence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom and/or disease control)
- •A representative formalin-fixed, paraffin-embedded tumor specimen in paraffin blocks, or at least 20 unstained slides with an associated pathology report documenting ER, PR, and HER2 negativity. Participants with fewer than 20 unstained slides available at baseline, and not fewer than 12 unstained slides will be eligible upon discussion with Medical Monitor
- •Eastern Cooperative Oncology Group performance status of 0 or 1
- •Measurable disease as defined by RECIST v1.1
- •Adequate hematologic and end-organ function
排除标准
- •Known central nervous system (CNS) disease, except for treated asymptomatic CNS metastases
- •Leptomeningeal disease
- •Pregnancy or lactation
- •History of autoimmune disease
- •Prior allogeneic stem cell or solid organ transplantation
- •Positive test for human immunodeficiency virus
- •Active hepatitis B or hepatitis C
- •Receipt of a live, attenuated vaccine within 4 weeks prior to randomization, during treatment, or within 5 months following the last dose of atezolizumab/placebo
研究组 & 干预措施
Atezolizumab Plus Nab-Paclitaxel
Participants assigned to atezolizumab plus nab-paclitaxel received both agents until disease progression or unacceptable toxicity.
干预措施: Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody (Drug)
Atezolizumab Plus Nab-Paclitaxel
Participants assigned to atezolizumab plus nab-paclitaxel received both agents until disease progression or unacceptable toxicity.
干预措施: Nab-Paclitaxel (Drug)
Placebo Plus Nab-Paclitaxel
Participants assigned to placebo plus nab-paclitaxel received both agents until disease progression or unacceptable toxicity.
干预措施: Nab-Paclitaxel (Drug)
Placebo Plus Nab-Paclitaxel
Participants assigned to placebo plus nab-paclitaxel received both agents until disease progression or unacceptable toxicity.
干预措施: Placebo (Drug)
结局指标
主要结局
OS in Participants With Detectable PD-L1
时间窗: Baseline until death due to any cause (up to approximately 58 months)
OS was defined as the time from the date of randomization to the date of death from any cause.
Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) in All Randomized Participants
时间窗: Baseline up to approximately 34 months
PFS was defined as the time from randomization to the occurrence of disease progression, as determined by investigators from tumor assessments per RECIST v1.1, or death from any cause, whichever occurred first.
Overall Survival (OS) in All Randomized Participants
时间窗: Baseline until death due to any cause (up to approximately 58 months)
OS was defined as the time from the date of randomization to the date of death from any cause.
PFS According to RECIST v1.1 in Participants With Detectable Programmed Death-Ligand 1 (PD-L1)
时间窗: Baseline up to approximately 34 months
PFS was defined as the time from randomization to the occurrence of disease progression, as determined by investigators from tumor assessments per RECIST v1.1, or death from any cause, whichever occurred first.
次要结局
- Percentage of Participants With an Objective Response of Complete Response (CR) or Partial Response (PR) According to RECIST v1.1 in All Randomized Participants(Baseline up to approximately 34 months)
- Percentage of Participants With an Objective Response of CR or PR According to RECIST v1.1 in Participants With Detectable PD-L1(Baseline up to approximately 34 months)
- Duration of Response (DOR) According to RECIST v1.1 in All Randomized Participants(Baseline up to approximately 34 months)
- DOR Acccording to RECIST v1.1 in Participants With Detectable PD-L1(Baseline up to approximately 34 months)
- Time to Deterioration (TTD) in Global Health Status/Health Related Quality of Life According to European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) v3.0 in All Randomized Participants(Baseline up to approximately 58 months)
- TTD in Global Health Status/Health Related Quality of Life According to EORTC QLQ-C30 v3.0 in Participants With Detectable PD-L1(Baseline up to approximately 58 months)
- Percentage of Participants With at Least One Adverse Event(Baseline up to to the data cutoff date: 31 August 2021 (up to approximately 74 months))
- Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab(Baseline up to approximately 53 months)
- Maximum Serum Concentration (Cmax) for Atezolizumab(Cycle 1 Day 1 (Cycle = 28 days))
- Minimum Serum Concentration (Cmin) for Atezolizumab(Day 27 of Cycle 1, 2, 3, and 7 (Cycle = 28 days))
- Plasma Concentrations of Total Paclitaxel(Pre-dose (Hour 0) on Cycle 1 Day 1, pre-dose (Hour 0), 5-10 minutes before end of nab-paclitaxel infusion, 1 hour after end of nab-paclitaxel infusion (infusion duration = 30 minutes) on Cycle 3 Day 1 (Cycle = 28 days))