An Open-Label Randomized Phase III Trial of BMS-936558 (Nivolumab) Versus Docetaxel in Previously Treated Advanced or Metastatic Squamous Cell Non-small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 272
- 试验地点
- 124
- 主要终点
- Overall Survival (OS) Rate in All Randomized Participants
研究概览
简要总结
The purpose of the study is to compare the overall survival of BMS-936558 as compared with Docetaxel in subjects with squamous cell non-small cell lung cancer (NSCLC), after failure of prior platinum-based chemotherapy.
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
- •Men and women ≥18 years of age
- •Subjects with histologically or cytologically-documented squamous cell NSCLC who present with Stage IIIB/IV disease or with recurrent or progressive disease following multimodal therapy (radiation therapy, surgical resection or definitive chemoradiation therapy for locally advanced disease)
- •Disease recurrence or progression during/after one prior platinum doublet-based chemotherapy regimen for advanced or metastatic disease
- •Measurable disease by computed tomography (CT)/Magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- •A formalin fixed, paraffin-embedded (FFPE) tumor tissue block or unstained slides of tumor sample (archival or recent) must be available for biomarker evaluation. Specimens must be received by the central lab prior to randomization. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is insufficient
排除标准
- •Subjects with untreated central nervous system (CNS) metastases are excluded. Subjects are eligible if CNS metastases are treated and subjects are neurologically returned to baseline for at least 2 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ≤10 mg daily prednisone (or equivalent)
- •Subjects with carcinomatous meningitis
- •Subjects with active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
- •Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of randomization
- •Prior therapy with anti-Programmed death-1 (PD-1), anti-Programmed cell death ligand 1 (PD-L1), anti-Programmed cell death ligand 2 (PD-L2), anti-CD137, or anti-Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
- •Prior treatment on the first line study CA184104 first line NSCLC study
- •Prior treatment with Docetaxel
- •Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
- •Treatment with any investigational agent within 14 days of first administration of study treatment
研究组 & 干预措施
Arm A: Nivolumab
Nivolumab 3 mg/kg solution intravenously (IV) every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
干预措施: Nivolumab (Biological)
Arm B: Docetaxel
Docetaxel 75 mg/m^2 concentrate for solution for intravenous infusion every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
干预措施: Docetaxel (Drug)
结局指标
主要结局
Overall Survival (OS) Rate in All Randomized Participants
时间窗: Randomization to 18 months post-randomization, up to June 2015
The overall survival rate is the probability that a participant will be alive at 6, 12, and 18 months following randomization. Overall survival was defined as the time between the date of randomization and the date of death as a result of any cause. Survival rates were determined via Kaplan-Meier estimates.
Overall Survival (OS) Time in Months for All Randomized Participants at Primary Endpoint
时间窗: Randomization until 199 deaths, up to November 2014, approximately 25 months
OS was defined as the time between the date of randomization and the date of death from any cause. Participants were censored at the date they were last known to be alive. Median OS time was calculated using Kaplan-Meier (KM) method. Hazard ratio (HR) and the corresponding Confidence Interval (CI) were estimated in a stratified Cox proportional hazards model for distribution of OS in each randomized arm. Interim analysis (Primary Endpoint) was planned to occur after at least 196 deaths, with the actual analysis occurring at 199 deaths.
Number of Deaths From Any Cause in All Randomized Participants at Primary Endpoint
时间窗: Randomization until 199 deaths, up to November 2014, approximately 25 months
The number of participants who died from any cause was reported for each arm. Interim analysis (Primary Endpoint) was planned to occur after at least 196 deaths, with the actual analysis occurring at 199 deaths.
次要结局
- Objective Response Rate (ORR) in All Randomized Participants(From the date of randomization up to the date of objectively documented progression, up to approximately 103 months)
- Progression Free Survival Rate (PFSR)(From randomization to specified timepoints, up to 84 months)
- Percentage of Participants Experiencing Disease-related Symptom Improvement by Week 12(From randomization up to Week 12)
- Objective Response Rate (ORR) by Baseline PD-L1 Expression for All Randomized Participants(From the date of randomization up to the date of objectively documented progression, up to approximately 103 months)
- Progression-Free Survival (PFS) Time in Months for All Randomized Participants(From randomization up to the first confirmed response to the date of the first documented tumor progression or death due to any cause, whichever occurred first, up to approximately 103 months)
- Overall Survival (OS) Time in Months by Baseline PD-L1 Expression for All Randomized Participants(From the date of randomization to the date of death from any cause, up to approximately 103 months)
- Progression Free Survival (PFS) Time in Months by Baseline PD-L1 Expression for All Randomized Participants(From the date of first confirmed response to the date of the first documented tumor progression or death due to any cause, whichever occurred first, up to approximately 103 months)
- Time To Response (TTR) in Months for All Confirmed Responders(From the date of randomization to the date of the first confirmed response, up to approximately 12 months)
- Duration of Objective Response (DOR) in Months for All Confirmed Responders(From the date of first confirmed response to the date of the first documented tumor progression or death due to any cause, whichever occurred first, up to approximately 94 months)