NCT03191786已完成3 期
A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab Compared With Chemotherapy in Patients With Treatment Naïve Advanced or Recurrent (Stage IIIb Not Amenable for Multimodality Treatment) or Metastatic (Stage IV) Non-Small Cell Lung Cancer Who Are Deemed Unsuitable for Platinum-Containing Therapy
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 453
- 试验地点
- 91
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
This Phase III, global, multicenter, open-label, randomized, controlled study will evaluate the efficacy and safety of atezolizumab (an anti-programmed death-ligand 1 [anti-PD-L1] antibody) compared with a single agent chemotherapy regimen by investigator choice (vinorelbine or gemcitabine) in treatment-naïve participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) who are deemed unsuitable for any platinum-doublet chemotherapy due to poor performance status (Eastern Cooperative Oncology Group [ECOG] performance status of 2-3).
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 diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC as per the American Joint Committee on Cancer (AJCC) 7th edition
- •No sensitizing epidermal growth factor receptor (EGFR) mutation (L858R or exon 19 deletions) or anaplastic lymphoma kinase (ALK) fusion oncogene detected
- •No prior systemic treatment for advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC as per the AJCC 7th edition
- •Life expectancy greater than or equal to (>/=) 8 weeks
- •Deemed unsuitable by the investigator for any platinum-doublet chemotherapy due to poor performance status (ECOG performance status of 2-3). However, participants >= 70 years of age who have an ECOG PS of 0 or 1 may be included due to: a) substantial comorbidities; b) contraindication(s) for any platinum-doublet chemotherapy
- •Representative formalin-fixed paraffin-embedded (FPPE) tumor tissue block obtained during course of disease (archival tissue) or at screening
- •Participants with treated, asymptomatic central nervous system (CNS) metastases are eligible, provided they meet all of the following criteria: Measurable disease outside CNS; Only supratentorial and cerebellar metastases allowed; No ongoing requirement for corticosteroids as therapy for CNS disease; No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to randomization; No evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study
- •Adequate hematologic and end organ function
- •Female participants of childbearing potential randomized to the atezolizumab treatment arm agree to use protocol defined methods of contraception
排除标准
- •Cancer-Specific Exclusion Criteria:
- •Participants younger than 70 years who have an ECOG performance status of 0 or 1
- •Active or untreated CNS metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation of the brain during screening and prior radiographic assessments
- •Uncontrolled tumor-related pain
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
- •Uncontrolled or symptomatic hyerpcalcemia (ionized calcium > 1.5 mmol/L or calcium >12 mg/dL or corrected serum calcium >ULN)
- •History of other malignancy within 5 years prior to screening, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
- •National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 (v4.0) Grade 3 or higher toxicities due to any prior therapy (example [e.g.], radiotherapy) (excluding alopecia), which have not shown improvement and are strictly considered to interfere with current study medication
- •Participants who have received prior neo-adjuvant, adjuvant chemotherapy, radiotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from randomization since the last chemotherapy, radiotherapy, or chemoradiotherapy
- •General Medical Exclusion Criteria:
- •History of autoimmune disease except autoimmune-related hypothyroidism and controlled Type I diabetes mellitus
- •History of idiopathic pulmonary fibrosis (IPF), organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis
- •Known positivity for human immunodeficiency virus (HIV)
- •Known active hepatitis B or hepatitis C
- •Active tuberculosis
- •Severe infections within 4 weeks prior to randomization
- •Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (Class II or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina
- •Major surgical procedure other than for diagnosis within 4 weeks prior to randomization or anticipation of need for a major surgical procedure during the course of the study
- •Prior allogeneic bone marrow transplantation or solid organ transplant
- •Participants with an illness or condition that may interfere with capacity or compliance with the study protocol, as per investigator's judgment
- •Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days prior to randomization
- •Exclusion Criteria Related to Atezolizumab:
- •History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- •Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
- •Oral or IV antibiotic treatment
- •Administration of a live, attenuated vaccine within 4 weeks before randomization or anticipation that such a live attenuated vaccine will be required during the study
- •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 antibodies
- •Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to randomization
- •Treatment with systemic corticosteroids or other immunosuppressive medications
- •Participants not willing to stop treatment with traditional herbal medicines
- •Exclusion Criteria Related to Chemotherapy:
- •Known sensitivity and contraindications to the 2 comparative chemotherapy agents (that is [i.e.] vinorelbine, oral or intravenous, and gemcitabine, intravenous)
研究组 & 干预措施
Atezolizumab
Experimental
Participants will receive atezolizumab 1200 milligrams (mg) intravenous (IV) infusion on Day 1 of each 21-day cycle until loss of clinical benefit, unacceptable toxicity, participant or physician decision to discontinue, or death.
干预措施: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody (Drug)
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
Active Comparator
Participants will receive single agent chemotherapy; either vinorelbine oral or IV, or gemcitabine IV, according to the label based on investigator's choice.
干预措施: Vinorelbine (Drug)
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
Active Comparator
Participants will receive single agent chemotherapy; either vinorelbine oral or IV, or gemcitabine IV, according to the label based on investigator's choice.
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: From randomization up to death from any cause (up to approximately 55 months)
OS was defined as the time between the date of randomization and the date of death due to any cause. Kaplan-Meier (KM) estimates were used to calculate median.
次要结局
- OS Rates at the 6, 12, 18, 24-Months Timepoints(6, 12, 18 and 24 months)
- Percentage of Participants With Objective Response, as Determined by the Investigator Using Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)(From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months))
- Progression-Free Survival (PFS), as Determined by the Investigator Using RECIST v1.1(From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months))
- Duration of Response (DOR), as Determined by the Investigator Using RECIST v1.1(Time from the first occurrence of a documented objective response to the time of disease progression or death from any cause, whichever occurs first (up to approximately 55 months))
- Percentage of Participants With At Least One Adverse Event (AE)(Baseline up to 90 days after last dose of atezolizumab (approximately 62 months))
- Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC-QLQ-C30) Score(Baseline, Day 1 of each treatment cycle up to 30 days after last dose (up to approximately 55 months) (Cycle length = 21 days))
- Change From Baseline in EORTC QLQ Supplementary Lung Cancer Module 13 (EORTC QLQ-LC13) Score(Baseline, Day 1 of each treatment cycle up to 30 days after last dose (up to approximately 55 months) (Cycle length = 21 days))
- Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms as Assessed by EORTC QLQ-C30 Score(From baseline up to approximately 55 months)
- TTD in Patient-Reported Lung Cancer Symptoms As Assessed by EORTC QLQ-LC13 Score(From baseline up to approximately 55 months)
- OS in Participants With Programmed Death-Ligand 1 (PD-L1) Positive Status(From randomization up to death from any cause (up to approximately 55 months))
- PFS as Determined by the Investigator Using RECIST v1.1 in Participants With PD-L1 Positive Status(From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months))
研究者
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