A Phase III, Open Label, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Compared With a Platinum Agent (Cisplatin or Carboplatin) in Combination With Either Pemetrexed or Gemcitabine for PD-L1-Selected, Chemotherapy-Naive Patients With Stage IV Non-Squamous Or Squamous Non-Small Cell Lung Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 572
- 试验地点
- 142
- 主要终点
- Overall Survival (OS) in the TC3 or IC3-WT Populations
研究概览
简要总结
This randomized, open-label study will evaluate the efficacy and safety of atezolizumab compared with chemotherapy consisting of a platinum agent (cisplatin or carboplatin per investigator discretion) combined with either pemetrexed (non-squamous disease) or gemcitabine (squamous disease) in programmed death-ligand 1 (PD-L1)-selected, chemotherapy-naive participants with Stage IV Non-Squamous or 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
- •Histologically or cytologically confirmed, Stage IV non-squamous or squamous NSCLC
- •No prior treatment for Stage IV non-squamous or squamous NSCLC. Participant known to have a sensitizing mutation in the epidermal growth factor receptor (EGFR) gene or an anaplastic lymphoma kinase (ALK) fusion oncogene are excluded from the study
- •Tumor PD-L1 expression as determined by immunohistochemistry (IHC) assay of archival tumor tissue or tissue obtained at screening
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
- •Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
- •Adequate hematologic and end-organ function
排除标准
- •Known sensitizing mutation in the EGFR gene or ALK fusion oncogene
- •Active or untreated central nervous system (CNS) metastases as determined by Computed Tomography (CT) or magnetic resonance imaging (MRI) evaluation
- •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 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 (CD) 137 agonists or immune checkpoint blockade therapies, anti PD1, 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
(Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)
Participants with non-squamous NSCLC will receive chemotherapy with pemetrexed in combination with either cisplatin or carboplatin (per investigator discretion) on Day 1 of each 21-day cycle for 4 or 6 cycles as per local standard of care, followed by maintenance therapy with pemetrexed alone as per local standard of care until disease progression (per RECIST v1.1), unacceptable toxicity, or death (maximum up to approximately 58 months). Participants with squamous NSCLC will receive chemotherapy with gemcitabine on Days 1 and 8 of each 21-day cycle in combination with either cisplatin or carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles as per local standard of care, followed by best supportive care as per local standard of care until disease progression, unacceptable toxicity, or death (maximum up to approximately 58 months).
干预措施: Carboplatin (Drug)
(Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)
Participants with non-squamous NSCLC will receive chemotherapy with pemetrexed in combination with either cisplatin or carboplatin (per investigator discretion) on Day 1 of each 21-day cycle for 4 or 6 cycles as per local standard of care, followed by maintenance therapy with pemetrexed alone as per local standard of care until disease progression (per RECIST v1.1), unacceptable toxicity, or death (maximum up to approximately 58 months). Participants with squamous NSCLC will receive chemotherapy with gemcitabine on Days 1 and 8 of each 21-day cycle in combination with either cisplatin or carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles as per local standard of care, followed by best supportive care as per local standard of care until disease progression, unacceptable toxicity, or death (maximum up to approximately 58 months).
干预措施: Cisplatin (Drug)
(Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)
Participants with non-squamous NSCLC will receive chemotherapy with pemetrexed in combination with either cisplatin or carboplatin (per investigator discretion) on Day 1 of each 21-day cycle for 4 or 6 cycles as per local standard of care, followed by maintenance therapy with pemetrexed alone as per local standard of care until disease progression (per RECIST v1.1), unacceptable toxicity, or death (maximum up to approximately 58 months). Participants with squamous NSCLC will receive chemotherapy with gemcitabine on Days 1 and 8 of each 21-day cycle in combination with either cisplatin or carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles as per local standard of care, followed by best supportive care as per local standard of care until disease progression, unacceptable toxicity, or death (maximum up to approximately 58 months).
干预措施: Gemcitabine (Drug)
(Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)
Participants with non-squamous NSCLC will receive chemotherapy with pemetrexed in combination with either cisplatin or carboplatin (per investigator discretion) on Day 1 of each 21-day cycle for 4 or 6 cycles as per local standard of care, followed by maintenance therapy with pemetrexed alone as per local standard of care until disease progression (per RECIST v1.1), unacceptable toxicity, or death (maximum up to approximately 58 months). Participants with squamous NSCLC will receive chemotherapy with gemcitabine on Days 1 and 8 of each 21-day cycle in combination with either cisplatin or carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles as per local standard of care, followed by best supportive care as per local standard of care until disease progression, unacceptable toxicity, or death (maximum up to approximately 58 months).
干预措施: Pemetrexed (Drug)
Atezolizumab
Participants with squamous or non-squamous NSCLC will receive atezolizumab on Day 1 of each 21-day cycle until loss of clinical benefit (as assessed by the investigator), unacceptable toxicity, or death (maximum up to approximately 58 months).
干预措施: Atezolizumab (MPDL3280A) [TECENTRIQ], an engineered anti-PDL1 antibody (Drug)
结局指标
主要结局
Overall Survival (OS) in the TC3 or IC3-WT Populations
时间窗: From randomization to death from any cause until data cut-off on 10 September 2018 (up to approximately 38 months)
OS is defined as the time from randomization to death from any cause.
Overall Survival (OS) in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations
时间窗: From randomization to death from any cause until data cut-off on 4 February 2020 (up to approximately 54.5 months)
OS is defined as the time from randomization to death from any cause.
次要结局
- OS in Participants With PD-L1 Expression(From randomization to death from any cause until data cut-off on 10 September 2018 (up to approximately 38 months))
- OS in Participants With Blood Tumor Mutational Burden (bTMB)(From randomization to death from any cause until data cut-off on 10 September 2018 (up to approximately 38 months))
- Progression-free Survival (PFS) in the TC3 or IC3-WT Populations(From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first until data cut-off on 10 September 2018 (up to approximately 38 months))
- Change From Baseline in Patient-reported Lung Cancer Symptoms Score as Assessed by the SILC Scale Symptom Score in the TC3 or IC3-WT Populations(Baseline until data cut-off on 10 September 2018 (up to approximately 38 months))
- Percentage of Participants Who Are Alive at 1 Year in the TC3 or IC3-WT Populations(Baseline to 1 year or death, whichever occurs first until data cut-off on 10 September 2018 (up to approximately 38 months))
- Percentage of Participants With at Least One Adverse Event(Baseline up to until data cut-off on 8 March 2022 (up to approximately 79.5 months))
- Progression-free Survival (PFS) in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations(From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first until data cut-off on 4 February 2020 (up to approximately 54.5 months))
- Percentage of Participants With Objective Response (ORR) in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations(Every 6 weeks for 48 weeks following Day 1, thereafter every 9 weeks after completion of Week 48 tumor assessment, regardless of treatment delays, until radiographic disease progression until data cut-off on 4 Feb 2020 (up to approximately 54.5 months))
- Duration of Response (DOR) in the TC3 or IC3-WT Populations(From first occurrence of a complete response or partial response, whichever occurs first, until first date that progressive disease or death is documented, whichever occurs first until data cut-off on 10 September 2018 (up to approximately 38 months))
- Duration of Response (DOR) in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations(From first occurrence of a complete response or partial response, whichever occurs first, until first date that progressive disease or death is documented, whichever occurs first until data cut-off on 4 February 2020 (up to approximately 54.5 months))
- Time to Deterioration (TTD) in Patient-reported Lung Cancer Symptoms Score as Assessed by the Symptoms in Lung Cancer (SILC) Scale Symptom Score in the TC3 or IC3-WT Populations(Baseline until data cut-off on 10 September 2018 (up to approximately 38 months))
- Minimum Observed Serum Concentration (Cmin) of Atezolizumab(Prior to infusion (0 hour) on Day 1 of Cycles 2, 3, 4, 8, 16, and every eighth cycle thereafter, and at treatment discontinuation until data cut-off on 10 September 2018 (up to approximately 38 months) (cycle duration = 21 days))
- Percentage of Participants With Objective Response (ORR) in the TC3 or IC3-WT Populations(Every 6 weeks for 48 weeks following Day 1, thereafter every 9 weeks after completion of Week 48 tumor assessment, regardless of treatment delays, until radiographic disease progression until data cut-off on 10 Sep 2018 (up to approximately 38 months))
- Percentage of Participants Who Are Alive at 2 Years in the TC3 or IC3-WT Populations(Baseline to 2 years or death, whichever occurs first until data cut-off on 10 September 2018 (up to approximately 38 months))
- Percentage of Participants Who Are Alive at 1 Year in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations(Baseline to 1 year or death, whichever occurs first until clinical cut-off date on 4 February 2020 (up to approximately 54.5 months))
- Percentage of Participants Who Are Alive at 2 Years in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations(Baseline to 2 years or death, whichever occurs first until clinical cut-off date on 4 February 2020 (up to approximately 54.5 months))
- TTD as Assessed Using EORTC QLQ Supplementary Lung Cancer Module (EORTC QLQ-LC13) in the TC3 or IC3-WT Populations(Baseline until data cut-off on 10 September 2018 (up to approximately 38 months))
- Investigator-Assessed PFS in Participants With bTMB According to RECIST v1.1(From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first until data cut-off on 10 September 2018 (up to approximately 38 months))
- Maximum Observed Serum Concentration (Cmax) of Atezolizumab(0 hour (predose) and 30 minutes after atezolizumab infusion on Day 1 (infusion duration = up to 1 hour))
- Investigator-Assessed PFS in Participants With PD-L1 Expression According to RECIST v1.1(From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first until data cut-off on 10 September 2018 (up to approximately 38 months))
- Percentage of Participants With Anti-therapeutic Antibodies (ATAs)(Baseline until data cut-off on 10 September 2018 (up to approximately 38 months))