A Phase III Multicenter, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Carboplatin+Nab-Paclitaxel for Chemotherapy-Naive Patients With Stage IV Non-Squamous Non-Small Cell Lung Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 723
- 试验地点
- 132
- 主要终点
- Progression-Free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in the ITT-WT Population
研究概览
简要总结
This randomized Phase III, multicenter, open-label study designed to evaluate the safety and efficacy of atezolizumab (an engineered anti-programmed death-ligand 1 [PD-L1] antibody) in combination with carboplatin+nab-paclitaxel compared with treatment with carboplatin+nab-paclitaxel in chemotherapy-naive participants with Stage IV non-squamous NSCLC. Participants were randomized in a 2:1 ratio to Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin) or Arm B (Nab-Paclitaxel+Carboplatin).
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
- •Eastern Cooperative Oncology Group performance status of 0 or 1
- •Histologically or cytologically confirmed, Stage IV non-squamous NSCLC
- •Participants with no prior treatment for Stage IV non-squamous NSCLC
- •Previously obtained archival tumor tissue or tissue obtained from fresh biopsy at screening
- •Measurable disease, as defined by RECIST v1.1
- •Adequate hematologic and end organ function
排除标准
- •Cancer-Specific Exclusions:
- •Active or untreated central nervous system metastases
- •Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
- •General Medical Exclusions:
- •Pregnant or lactating women
- •History of autoimmune disease
- •History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
- •Positive test for human immunodeficiency virus
- •Active hepatitis B or hepatitis C
- •Severe infection within 4 weeks prior to randomization
- •Significant cardiovascular disease
- •Illness or condition that interferes with the participant's capacity to understand, follow and/or comply with study procedures
- •Exclusion Criteria Related to Medications:
- •Prior treatment with cluster of differentiation 137 agonists or immune checkpoint blockade therapies, anti-programmed death-1, and anti-PD-L1 therapeutic antibodies
研究组 & 干预措施
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)
Participants received intravenous (IV) infusion of atezolizumab and carboplatin on Day 1 of each 21-day cycle, and nab-paclitaxel on Days 1, 8, and 15 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurred first during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.
干预措施: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody (Drug)
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)
Participants received intravenous (IV) infusion of atezolizumab and carboplatin on Day 1 of each 21-day cycle, and nab-paclitaxel on Days 1, 8, and 15 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurred first during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.
干预措施: Carboplatin (Drug)
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)
Participants received intravenous (IV) infusion of atezolizumab and carboplatin on Day 1 of each 21-day cycle, and nab-paclitaxel on Days 1, 8, and 15 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurred first during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.
干预措施: Nab-Paclitaxel (Drug)
Arm B (Nab-Paclitaxel+Carboplatin)
Participants received IV infusion of carboplatin on Day 1 and nab-paclitaxel on Days 1, 8, and 15 of each 21-day cycle for 4 or 6 cycles or until disease progression whichever occurred first during induction treatment phase. Participants received best supportive care during maintenance treatment phase. Switch maintenance to pemetrexed was also permitted. Participants who were consented prior to approval of protocol Version 5 were given the option to cross over to receive atezolizumab as monotherapy until disease progression.
干预措施: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody (Drug)
Arm B (Nab-Paclitaxel+Carboplatin)
Participants received IV infusion of carboplatin on Day 1 and nab-paclitaxel on Days 1, 8, and 15 of each 21-day cycle for 4 or 6 cycles or until disease progression whichever occurred first during induction treatment phase. Participants received best supportive care during maintenance treatment phase. Switch maintenance to pemetrexed was also permitted. Participants who were consented prior to approval of protocol Version 5 were given the option to cross over to receive atezolizumab as monotherapy until disease progression.
干预措施: Carboplatin (Drug)
Arm B (Nab-Paclitaxel+Carboplatin)
Participants received IV infusion of carboplatin on Day 1 and nab-paclitaxel on Days 1, 8, and 15 of each 21-day cycle for 4 or 6 cycles or until disease progression whichever occurred first during induction treatment phase. Participants received best supportive care during maintenance treatment phase. Switch maintenance to pemetrexed was also permitted. Participants who were consented prior to approval of protocol Version 5 were given the option to cross over to receive atezolizumab as monotherapy until disease progression.
干预措施: Nab-Paclitaxel (Drug)
Arm B (Nab-Paclitaxel+Carboplatin)
Participants received IV infusion of carboplatin on Day 1 and nab-paclitaxel on Days 1, 8, and 15 of each 21-day cycle for 4 or 6 cycles or until disease progression whichever occurred first during induction treatment phase. Participants received best supportive care during maintenance treatment phase. Switch maintenance to pemetrexed was also permitted. Participants who were consented prior to approval of protocol Version 5 were given the option to cross over to receive atezolizumab as monotherapy until disease progression.
干预措施: Pemetrexed (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in the ITT-WT Population
时间窗: Up to approximately 35 months after first patient enrolled
PFS is defined as the time between the date of randomization and the date of first documented disease progression as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurs first in the ITT-WT population.
Overall Survival (OS) in the ITT-WT Population
时间窗: Up to approximately 35 months after first patient enrolled
OS is defined as the time between the date of randomization and date of death from any cause in the ITT-WT population.
次要结局
- Event Free Rate (%) at Year 1 and 2 in ITT-WT Population and ITT Population(Up to 41 months after first patient enrolled, years 1 and 2 reported)
- OS as Determined by the Investigator Using Recist v1.1 in the ITT Population(Up to approximately 41 months after first subject enrolled)
- OS as Determined by the Investigator Using RECIST v1.1 in the PD-L1 Expression Population and PD-L1 Expression WT Population(Up to approximately 35 months after first patient enrolled)
- Percentage of Participants With an Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator Using RECIST v1.1 in the ITT-WT Population(Up to approximately 41 months after first subject enrolled)
- Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1 in ITT-WT Population, ITT Population, and PD-L1 Expression Population and PD-L1 Expression WT Population(Up to approximately 35 months after first subject enrolled)
- Event Free Rate (%) at Year 1 and 2 in PD-L1 Expression Population and PD-L1 Expression WT Population(Up to 35 months after first patient enrolled, years 1 and 2 reported)
- Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms in the ITT-WT Population(Up to approximately 35 months after first subject enrolled)
- PFS as Determined by the Investigator Using Recist v1.1 in the ITT Population, PD-L1 Expression Population, and PD-L1 Expression WT Population(Up to approximately 35 months after first subject enrolled)
- Percentage of Participants With an Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator Using RECIST v1.1 in the ITT Population, PD-L1 Expression Population, and PD-L1 Expression WT Population(Up to approximately 35 months after first subject enrolled)
- Change From Baseline in Patient-Reported Lung Cancer Symptoms Score Using the Symptoms in Lung Cancer (SILC) Scale(Up to approximately 35 months after first subject enrolled)
- Percentage of Participants With Adverse Events(Up to approximately 69 months after first patient enrolled)
- Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab(Up to approximately 35 months after first subject enrolled)
- Maximum Observed Serum Concentration (Cmax) of Atezolizumab for Patients in Atezolizumab+Carboplatin+Nab-Paclitaxel Arm(Cycle 1 Day 1 and Cycle 3 Day 1 (Cycle length = 21 days))
- Minimum Observed Serum Concentration (Cmin) of Atezolizumab Prior to Infusion in Atezolizumab+Carboplain+Nab-Paclitaxel(Cycle 1 Day 21, Cycle 2 Day 21, Cycle 3 Day 21, and Cycle 7 Day 21 (Cycle length = 21 days))
- Plasma Concentrations of Carboplatin(Predose (same day of treatment administration), 5-10 minutes before end of carboplatin infusion, 1 hour after carboplatin infusion (infusion duration=15 to 30 minutes) on Day 1 of Cycle 1 and 3 (1 Cycle=21 days) (up to approximately 35 months))
- Plasma Concentrations of Nab-Paclitaxel Reported as Total Paclitaxel(Predose (same day of treatment administration), 5-10 minutes before end of nab-paclitaxel infusion, 1 hour after nab-paclitaxel infusion (infusion duration=30 minutes) on Day 1 of Cycle 1 and 3 (1 Cycle=21 days) (up to approximately 35 months))