A Phase III, Open-Label, Randomized Study of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Carboplatin+Paclitaxel With or Without Bevacizumab Compared With Carboplatin + Paclitaxel + Bevacizumab in Chemotherapy-Naïve 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
- 1,202
- 试验地点
- 240
- 主要终点
- Overall Survival (OS) in Arm B Versus Arm C in ITT-WT Population
研究概览
简要总结
This randomized, open-label study evaluated the safety and efficacy of atezolizumab (an engineered anti-programmed death-ligand 1 [PD-L1] antibody) in combination with carboplatin+paclitaxel with or without bevacizumab compared with treatment with carboplatin+paclitaxel+bevacizumab in chemotherapy-naïve participants with Stage IV non-squamous NSCLC. Participants were randomized in a 1:1:1 ratio to Arm A (Atezolizumab+Carboplatin+Paclitaxel), Arm B (Atezolizumab+Carboplatin+Paclitaxel+Bevacizumab), or Arm C (Carboplatin+Paclitaxel+Bevacizumab).
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 0 or 1
- •Histologically or cytologically confirmed, Stage IV non-squamous NSCLC
- •Participants with no prior treatment for Stage IV non-squamous NSCLC
- •Known PD-L1 status as determined by immunohistochemistry assay performed on previously obtained archival tumor tissue or tissue obtained from a 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+Paclitaxel+Carboplatin)
Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs 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+Paclitaxel+Carboplatin)
Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs 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+Paclitaxel+Carboplatin)
Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.
干预措施: Paclitaxel (Drug)
Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
干预措施: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody (Drug)
Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
干预措施: Bevacizumab (Drug)
Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
干预措施: Carboplatin (Drug)
Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
干预措施: Paclitaxel (Drug)
Arm C (Bevacizumab+Paclitaxel+Carboplatin)
Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.
干预措施: Bevacizumab (Drug)
Arm C (Bevacizumab+Paclitaxel+Carboplatin)
Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.
干预措施: Carboplatin (Drug)
Arm C (Bevacizumab+Paclitaxel+Carboplatin)
Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Overall Survival (OS) in Arm B Versus Arm C in ITT-WT Population
时间窗: Baseline until death until data cut-off on 22 January 2018 (up to approximately 34 months)
Overall Survival (OS) in Arm B Versus Arm C in ITT-WT Population
Overall Survival (OS) in Arm A Versus Arm C in ITT-WT Population
时间窗: Baseline until death (up approximately 53 months)
Overall Survival (OS) in Arm A Versus Arm C in ITT-WT Population
Progression Free Survival (PFS), as Determined by the Investigator in Arm B Versus Arm C in the Teff-high WT Population and ITT-WT Population
时间窗: Baseline until disease progression or death, whichever occurs first until data cut-off on 15 September 2017 (up to approximately 29 months)
Progression Free Survival (PFS), as Determined by the Investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Arm B versus Arm C in the T-effector (Teff)-high wild type (WT) population and the intent-to-treat (ITT)-WT population.
次要结局
- PFS, as Determined by the Investigator in Arm B Versus Arm C in Teff High Population and ITT Population(Baseline until disease progression or death, whichever occurs first (up to approximately 29 months))
- PFS, as Determined by the Investigator in Arm A Versus Arm B in Teff High-WT Population and ITT-WT Population(Baseline until disease progression or death, whichever occurs first (up to approximately 29 months))
- PFS, as Determined by the Investigator in Arm B Versus Arm C by PD-L1 Subgroup(Baseline until disease progression or death, whichever occurs first (up to approximately 29 months))
- OS in Arm B Versus Arm C by PD-L1 Subgroup(Baseline until death (up to approximately 34 months))
- OS in Arm A Versus Arm C by PD-L1 Subgroup(Baseline until death (up approximately 53 months))
- OS in Arm B Versus Arm C in Teff High-WT Population, Teff High Population, and ITT Population(Baseline until death (up to approximately 34 months))
- OS in Arm A Versus Arm C in Teff High-WT Population, Teff High Population, and ITT Population(Baseline until death (up approximately 53 months))
- OS in Arm A Versus Arm B in Teff High-WT Population and ITT-WT Population(Baseline until death (up approximately 53 months))
- Duration of Response (DOR), as Determined By Investigator in Arm B Versus Arm C(Baseline until disease progression or death, whichever occurs first (up to approximately 29 months))
- Percentage of Participants With an Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator in the Teff-High-WT Population and ITT-WT Population(Baseline until disease progression or death, whichever occurs first (up to approximately 29 months))
- OS Rates at Years 1 and 2 in Arm B Versus Arm C(Baseline to 2 years or death, whichever occurs first.)
- OS Rates at Years 1 and 2 in Arm A Versus Arm C(Baseline to 2 years or death, whichever occurs first.)
- Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms Determined by European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core 30 (QLQ-C30) Score(Baseline up to approximately 29 months)
- TTD in Patient-Reported Lung Cancer Symptoms as Determined by EORTC Quality-of-Life Questionnaire-Core Lung Cancer Module 13 (QLQ-LC13) Score(Baseline up to approximately 29 months)
- PFS, as Determined by the Independent Review Facility (IRF) in Arm B Versus Arm C in Teff-High-WT Population and ITT-WT Population(Baseline until disease progression or death, whichever occurs first (up to approximately 29 months))
- Change From Baseline in Patient-Reported Lung Cancer Symptoms Score Using the Symptoms in Lung Cancer (SILC) Scale(Baseline up to approximately 29 months)
- Percentage of Participants With Adverse Events(Baseline up to data cutoff date 7 December 2020 (up to approximately 68 months))
- Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab(Baseline up to approximately 29 months)
- Maximum Observed Serum Concentration (Cmax) of Atezolizumab in Arm A and Arm B(Day 1 of Cycle 1 and 3 (Cycle length=21 days))
- Minimum Observed Serum Concentration (Cmin) of Atezolizumab Prior to Infusion in Arm A and Arm B(Day 21 of Cycles 1, 2 3, and 7 (Cycle length=21 days))
- Plasma Concentrations for Carboplatin in Arm A, Arm B, and Arm C(Predose (same day of treatment administration), 5-10 minutes before end of carboplatin infusion, 1 h after carboplatin infusion (infusion duration=15 to 30 minutes) on D1 of Cy1,3 (Cycle length=21 days))
- Plasma Concentrations for Paclitaxel in Arm A, Arm B, and Arm C(Predose (same day of treatment administration), 5-10 minutes before end of paclitaxel infusion, 1 h after paclitaxel infusion (infusion duration=3 h) on D1 of Cy1,3 (Cycle length=21 days))
- Cmax of Bevacizumab in Arm B and Arm C(Cycle 1 Day 1 and Cycle 3 Day 1 (Cycle length=21 days))
- Cmin of Bevacizumab in Arm B and Arm C(Cycle 1 Day 1 and Cycle 2 Day 21 (Cycle length=21 days))