A Phase III, Open-Label, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Carboplatin+Paclitaxel or Atezolizumab in Combination With Carboplatin+Nab-Paclitaxel Versus Carboplatin+Nab-Paclitaxel in Chemotherapy-Naive Patients With Stage IV Squamous Non-Small Cell Lung Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,021
- 试验地点
- 242
- 主要终点
- Overall Survival (OS) in the ITT Population
研究概览
简要总结
This randomized, open-label study will evaluate the safety and efficacy of atezolizumab (MPDL3280A) in combination with carboplatin + paclitaxel or carboplatin + nab-paclitaxel compared with treatment with carboplatin + nab-paclitaxel in chemotherapy-naive participants with Stage IV squamous NSCLC.
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 (ECOG) performance status 0 or 1
- •Histologically or cytologically confirmed, treatment-naïve Stage IV squamous NSCLC
- •Previously obtained archival tumor tissue or tissue obtained from biopsy at screening
- •Measurable disease as defined by RECIST v1.1
- •Adequate hematologic and end organ function
排除标准
- •Active or untreated central nervous system (CNS) metastasis
- •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
- •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 (CT) scan, History of radiation pneumonitis in the radiation field (fibrosis) is permitted
- •Positive test for Human Immunodeficiency Virus (HIV)
- •Active hepatitis B or hepatitis C
- •Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibody
- •Severe infection within 4 weeks prior to randomization
- •Significant history of cardiovascular disease
研究组 & 干预措施
Arm A: Atezolizumab + Paclitaxel + Carboplatin
The induction phase of the study will consist of four or six cycles; atezolizumab, paclitaxel, and carboplatin will be administered on Day 1 of each 21-day cycle. The Day 1 order of drug administration is as follows: atezolizumab, then paclitaxel, then carboplatin. Participants who experience no further clinical benefit at any time during the induction phase will discontinue all study treatments. In the absence of the above criteria, after the 4- or 6-cycle induction phase, participants will begin maintenance therapy with atezolizumab. Atezolizumab will be continued as long as there is a clinical benefit to the participant.
干预措施: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (anti-PD-L1) antibody (Drug)
Arm A: Atezolizumab + Paclitaxel + Carboplatin
The induction phase of the study will consist of four or six cycles; atezolizumab, paclitaxel, and carboplatin will be administered on Day 1 of each 21-day cycle. The Day 1 order of drug administration is as follows: atezolizumab, then paclitaxel, then carboplatin. Participants who experience no further clinical benefit at any time during the induction phase will discontinue all study treatments. In the absence of the above criteria, after the 4- or 6-cycle induction phase, participants will begin maintenance therapy with atezolizumab. Atezolizumab will be continued as long as there is a clinical benefit to the participant.
干预措施: Carboplatin (Drug)
Arm A: Atezolizumab + Paclitaxel + Carboplatin
The induction phase of the study will consist of four or six cycles; atezolizumab, paclitaxel, and carboplatin will be administered on Day 1 of each 21-day cycle. The Day 1 order of drug administration is as follows: atezolizumab, then paclitaxel, then carboplatin. Participants who experience no further clinical benefit at any time during the induction phase will discontinue all study treatments. In the absence of the above criteria, after the 4- or 6-cycle induction phase, participants will begin maintenance therapy with atezolizumab. Atezolizumab will be continued as long as there is a clinical benefit to the participant.
干预措施: Paclitaxel (Drug)
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin
The induction phase of the study will consist of four or six cycles; atezolizumab and carboplatin will be administered on Day 1 of each 21-day cycle. Nab-Paclitaxel will be administered on Days 1, 8, and 15 of each 21-day cycle. The Day 1 order of drug administration is as follows: atezolizumab, then nab-paclitaxel, then carboplatin. Participants who experience no further clinical benefit at any time during the induction phase will discontinue all study treatments. In the absence of the above criteria, after the 4- or 6-cycle induction phase, participants will begin maintenance therapy with atezolizumab. Atezolizumab will be continued as long as there is a clinical benefit to the participant.
干预措施: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (anti-PD-L1) antibody (Drug)
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin
The induction phase of the study will consist of four or six cycles; atezolizumab and carboplatin will be administered on Day 1 of each 21-day cycle. Nab-Paclitaxel will be administered on Days 1, 8, and 15 of each 21-day cycle. The Day 1 order of drug administration is as follows: atezolizumab, then nab-paclitaxel, then carboplatin. Participants who experience no further clinical benefit at any time during the induction phase will discontinue all study treatments. In the absence of the above criteria, after the 4- or 6-cycle induction phase, participants will begin maintenance therapy with atezolizumab. Atezolizumab will be continued as long as there is a clinical benefit to the participant.
干预措施: Carboplatin (Drug)
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin
The induction phase of the study will consist of four or six cycles; atezolizumab and carboplatin will be administered on Day 1 of each 21-day cycle. Nab-Paclitaxel will be administered on Days 1, 8, and 15 of each 21-day cycle. The Day 1 order of drug administration is as follows: atezolizumab, then nab-paclitaxel, then carboplatin. Participants who experience no further clinical benefit at any time during the induction phase will discontinue all study treatments. In the absence of the above criteria, after the 4- or 6-cycle induction phase, participants will begin maintenance therapy with atezolizumab. Atezolizumab will be continued as long as there is a clinical benefit to the participant.
干预措施: Nab-Paclitaxel (Drug)
Arm C: Nab-Paclitaxel + Carboplatin
The induction phase of the study will consist of four or six cycles; carboplatin will be administered on Day 1 of each 21-day cycle, nab-paclitaxel will be administered on Days 1, 8, and 15 of each 21-day cycle. The Day 1 order of drug administration is as follows: nab-paclitaxel, then carboplatin. Participants who experience disease progression at any time during the induction phase will discontinue all study treatment. In the maintenance phase, participants will receive best supportive care.
干预措施: Carboplatin (Drug)
Arm C: Nab-Paclitaxel + Carboplatin
The induction phase of the study will consist of four or six cycles; carboplatin will be administered on Day 1 of each 21-day cycle, nab-paclitaxel will be administered on Days 1, 8, and 15 of each 21-day cycle. The Day 1 order of drug administration is as follows: nab-paclitaxel, then carboplatin. Participants who experience disease progression at any time during the induction phase will discontinue all study treatment. In the maintenance phase, participants will receive best supportive care.
干预措施: Nab-Paclitaxel (Drug)
结局指标
主要结局
Overall Survival (OS) in the ITT Population
时间窗: Up to approximately 39 months after first participant enrolled
OS is defined as the time between the date of randomization and date of death from any cause in the ITT population.
Progression Free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in the Intent-to-Treat (ITT) Population
时间窗: Up to approximately 30 months after first participant enrolled
PFS is defined as the time between the date of randomization and the date of first documented disease progression or death, whichever occurs first, in the ITT population.
次要结局
- PFS as Determined by the Investigator Using RECIST v1.1 in the TC1/2/3 or IC1/2/3 Population(Up to approximately 30 months after first participant enrolled)
- OS in the TC2/3 or IC2/3 Population(Up to approximately 39 months after first participant enrolled)
- Maximum Observed Serum Atezolizumab Concentration (Cmax)(Cycle 1 Day 1 and Cycle 3 Day 1 (Cycle length = 21 days))
- OS in the TC1/2/3 or IC1/2/3 Population(Up to approximately 39 months after first participant enrolled)
- Percentage of Participants With Objective Response as Determined by the Investigator Using RECIST v1.1 in the ITT Population(Up to approximately 30 months after first participant enrolled)
- Percentage of Participants With Adverse Events(Up to approximately 68 months after first participant enrolled)
- Percentage of Participants With Anti-therapeutic Antibody (ATA) Response to Atezolizumab(Up to approximately 30 months after first participant enrolled)
- PFS as Determined by the Investigator Using RECIST v1.1 in the ITT Population (Arm A and Arm B)(Up to approximately 30 months after first participant enrolled)
- Plasma Concentrations for Paclitaxel(Prior to infusion (within same day of treatment administration), 5-10 minutes before the end of infusion, and 1 hour after the end of infusion (infusion duration 180 minutes) on Day 1 of Cycles 1 and 3 (each cycle is 21 days))
- Plasma Concentrations for Carboplatin(Prior to infusion (within same day of treatment administration), 5-10 minutes before the end of infusion, and 1 hour after the end of infusion (infusion duration 15 to 30 minutes) on Day 1 of Cycles 1 and 3 (each cycle is 21 days))
- OS in the in the Teff Population(Up to approximately 39 months after first participant enrolled)
- PFS as Determined by the Investigator Using RECIST v1.1 in the Teff Population(Up to approximately 30 months after first participant enrolled)
- PFS as Determined by the Investigator Using RECIST v1.1 in the Tumor Cell (TC) 2/3 or Tumor-Infiltrating Immune Cell (IC) 2/3 Population(Up to approximately 30 months after first participant enrolled)
- Plasma Concentrations for Nab-Paclitaxel(Prior to infusion (within same day of treatment administration), 5-10 minutes before the end of infusion, and 1 hour after the end of infusion (infusion duration 30 minutes) on Day 1 of Cycles 1 and 3 (each cycle is 21 days))
- Minimum Observed Serum Atezolizumab Concentration (Cmin)(Predose on Day 1 of Cycles 1-4, 8, 16, every 8 cycle thereafter (up to 30 months), at treatment discontinuation (up to 30 months), and at 120 days after the last dose of atezolizumab (up to approximately 30 months, each cycle is 21 days))
- Duration of Response as Determined by the Investigator Using RECIST v1.1 in the ITT Population(Up to approximately 30 months after first participant enrolled)
- Event Free Rate at 1 and 2 Years in the ITT Population(1 and 2 years)
- Time to Deterioration (TTD) in Patient-reported Lung Cancer Symptoms Using EORTC QLQ-C30 Symptom Subscales in the ITT Population(Up to approximately 30 months after first participant enrolled)
- TTD in Patient-reported Lung Cancer Symptoms Using EORTC QLQ-LC13 Symptom Subscales in the ITT Population(Up to approximately 30 months after the first participant enrolled)
- Change From Baseline in Patient-reported Lung Cancer Symptoms Score Using the SILC Scale Symptom Severity Score in the ITT Population(Baseline up to approximately 30 months after first participant enrolled)
- OS in the ITT Population (Arm A and Arm B)(Up to approximately 39 months after first participant enrolled)