A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab (Anti-PD-L1 Antibody) Compared With Docetaxel in Patients With Non-Small Cell Lung Cancer After Failure With Platinum Containing Chemotherapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,225
- 试验地点
- 208
- 主要终点
- Percentage of Participants Who Died: PP-ITT
研究概览
简要总结
This global, multicenter, open-label, randomized, controlled study evaluated the efficacy and safety of atezolizumab (an anti-programmed death-ligand 1 [anti-PD-L1] antibody)compared with docetaxel in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure with platinum-containing chemotherapy. Participants were randomized 1:1 to receive either docetaxel or atezolizumab. Treatment may continue as long as participants experienced clinical benefit as assessed by the investigator, i.e., in the absence of unacceptable toxicity or symptomatic deterioration attributed to disease progression.
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
- •Locally advanced or metastatic (Stage IIIB, Stage IV, or recurrent) NSCLC
- •Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens
- •Disease progression during or following treatment with a prior platinum-containing regimen for locally advanced, unresectable/inoperable or metastatic NSCLC or disease recurrence within 6 months of treatment with a platinum-based adjuvant/neoadjuvant regimen or combined modality (e.g., chemoradiation) regimen with curative intent
- •Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
排除标准
- •Known active or untreated central nervous system (CNS) metastases
- •Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome
- •History of autoimmune disease
- •History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
- •Active hepatitis B or hepatitis C
- •Prior treatment with docetaxel
- •Prior treatment with cluster of differentiation 137 (CD137) agonists, anti-cytotoxic-T-lymphocyte-associated antigen 4 (anti-CTLA4), anti-programmed death-1 (anti-PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents
研究组 & 干预措施
Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody
Atezolizumab 1200 milligrams (mg) was administered via intravenous (IV) infusion on Day 1 of each 21-day cycle until disease progression, death, unacceptable toxicity, withdrawal of consent, or study termination by sponsor, whichever occurs first.
干预措施: Atezolizumab (Drug)
Docetaxel
Docetaxel 75 milligrams per meter square (mg/m^2) was administered via IV infusion on Day 1 of each 21-day cycle until disease progression, death, unacceptable toxicity, withdrawal of consent, or study termination by sponsor, whichever occurs first.
干预措施: Docetaxel (Drug)
结局指标
主要结局
Percentage of Participants Who Died: PP-ITT
时间窗: Baseline until death due to any cause (up to approximately 2.25 years)
OS: TC1/2/3 Or IC1/2/3 Subgroup of SP
时间窗: Baseline until death from any cause (approximately 2.87 years)
OS duration is defined as the difference in time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Participants who had no post-baseline information were censored at the date of randomization plus 1 day. OS was estimated using KM methodology.
Overall Survival (OS): PP-ITT
时间窗: Baseline until death due to any cause (up to approximately 2.25 years)
OS duration is defined as the difference in time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Participants who had no post-baseline information were censored at the date of randomization plus 1 day. OS was estimated using KM methodology.
OS: TC2/3 or IC2/3 Subgroup of SP
时间窗: Baseline until death due to any cause (up to approximately 2.87 years)
OS duration is defined as the difference in time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Participants who had no post-baseline information were censored at the date of randomization plus 1 day. OS was estimated using KM methodology.
Percentage of Participants Who Died: Tumor Cells (TC)1/2/3 or Tumor-Infiltrating Immune Cells (IC)1/2/3 Subgroup of PP
时间窗: Baseline until death due to any cause (up to approximately 2.25 years)
Percentage of participants who died among TC1/2/3 or IC1/2/3 subgroup of PP-ITT were reported. TC1 = presence of discernible programmed death-ligand 1 (PD-L1) staining of any intensity in \>/=1% and \<5% TCs; TC2: presence of discernible PD-L1 staining of any intensity in \>/=5% and \<50% TCs; TC3 = presence of discernible PD-L1 staining of any intensity in \>/=50% TCs; IC1 = presence of discernible PD-L1 staining of any intensity in ICs covering between \>/=1% and \<5% of tumor area occupied by tumor cells, associated intratumoral, and contiguous peri-tumoral desmoplastic stroma; IC2 = presence of discernible PD-L1 staining of any intensity in ICs covering between \>/=5% and \<10% of tumor area occupied by tumor cells, associated intratumoral, and contiguous peri-tumoral desmoplastic stroma; IC3 = presence of discernible PD-L1 staining of any intensity in ICs covering \>/=10% of tumor area occupied by tumor cells, associated intratumoral, and contiguous peri-tumoral desmoplastic stroma.
OS: TC1/2/3 or IC1/2/3 Subgroup of PP
时间窗: Baseline until death due to any cause (up to approximately 2.25 years)
OS duration is defined as the difference in time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Participants who had no post-baseline information were censored at the date of randomization plus 1 day. OS was estimated using KM methodology.
OS: SP-ITT
时间窗: Baseline until death due to any cause (up to approximately 2.87 years)
OS duration is defined as the difference in time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Participants who had no post-baseline information were censored at the date of randomization plus 1 day. OS was estimated using KM methodology.
OS: TC3 or IC3 Subgroup of SP
时间窗: Baseline until death due to any cause (up to approximately 2.87 years)
OS duration is defined as the difference in time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Participants who had no post-baseline information were censored at the date of randomization plus 1 day. OS was estimated using KM methodology.
次要结局
- Percentage of Participants With Objective Response as Determined Using RECIST v1.1: TC1/2/3 or IC1/2/3 Subgroup of PP(Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 2.25 years))
- DOR as Determined by Investigator Using RECIST v1.1: TC1/2/3 or IC1/2/3 Subgroup of PP(From first objective response of CR or PR to PD or death due to any cause, whichever occurred first (up to approximately 2.25 years))
- Percentage of Participants With Disease Progression (PD) as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Death: PP-ITT(Baseline up to PD or Death (up to approximately 2.25 years))
- Duration of Response (DOR) as Determined by Investigator Using RECIST v1.1: PP-ITT(From first objective response of CR or PR to PD or death due to any cause, whichever occurred first (up to approximately 2.25 years))
- EORTC QLQ-C30 Questionnaire Score: GHS Scale(Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days))
- Percentage of Participants With PD as Determined by Investigator Using RECIST v1.1 or Death: TC1/2/3 or IC1/2/3 Subgroup of PP(Baseline up to PD or Death (up to approximately 2.25 years))
- Progression-Free Survival (PFS) as Determined by Investigator Using RECIST v1.1: PP-ITT(Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 2.25 years))
- EORTC QLQ Core 30 (C30) Questionnaire Score: Single Items(Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days))
- EORTC QLQ-LC13 Questionnaire Score: Coughing(Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days))
- PFS as Determined by Investigator Using RECIST v1.1: TC1/2/3 or IC1/2/3 Subgroup of PP(Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 2.25 years))
- Percentage of Participants With Objective Response as Determined Using RECIST v1.1: PP-ITT(Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 2.25 years))
- Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms, Using the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire (QLQ) Lung Cancer Supplemental Module 13 (LC13)(Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years) (1 Cycle = 21 days))
- Minimum Observed Serum Atezolizumab Concentration (Cmin)(Predose (Hr 0) on Day 1 of Cycles 1, 2, 3, 4, 8, 16, 24, 32, EOT (approximately 2.25 years); 120 days after EOT (approximately 2.25 years) (1 Cycle=21 days))
- Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab(Baseline up to approximately 2.25 years (assessed at predose [Hour {Hr} 0] on Day 1 of Cycles 1, 2, 3, 4, 8, 16, then every 8 cycles up to end of treatment (EOT) [approximately 2.25 years]; 120 days after EOT [approximately 2.25 years] [1 Cycle=21 days]))
- Maximum Observed Serum Atezolizumab Concentration (Cmax)(Predose (Hr 0), 30 minutes (min) post-infusion (infusion duration: 60 min) on Cycle 1 Day 1 (1 Cycle=21 days))
- EORTC QLQ-LC13 Questionnaire Score: Hemoptysis(Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days))
- EORTC QLQ-LC13 Questionnaire Score: Pain in Arm or Shoulder(Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days))
- EORTC QLQ-C30 Questionnaire Score: Functional Subscales(Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days))
- EORTC QLQ-C30 Questionnaire Score: Symptom Subscale(Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days))
- EORTC QLQ-LC13 Questionnaire Score: Alopecia(Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days))
- EORTC QLQ-LC13 Questionnaire Score: Dysphagia(Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days))
- EORTC QLQ-LC13 Questionnaire Score: Dyspnea(Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days))
- PFS as Determined by Investigator Using RECIST v1.1: SP-ITT(Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 2.87 years))
- EORTC QLQ-LC13 Questionnaire Score: Pain in Chest(Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days))
- EORTC QLQ-LC13 Questionnaire Score: Peripheral Neuropathy(Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days))
- EORTC QLQ-LC13 Questionnaire Score: Pain in Other Parts(Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days))
- EORTC QLQ-LC13 Questionnaire Score: Sore Mouth(Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days))
- Percentage of Participants With Objective Response as Determined Using RECIST v1.1: SP-ITT(Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 2.87 years))
- DOR as Determined by Investigator Using RECIST v1.1: SP ITT(From first objective response of CR or PR to PD or death due to any cause, whichever occurred first (up to approximately 2.87 years))