A Randomized, Open-Label, Phase 3 Study of Nivolumab (BMS-936558) vs. Everolimus in Subjects With Advanced or Metastatic Clear-Cell Renal Cell Carcinoma Who Have Received Prior Anti-Angiogenic Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 821
- 试验地点
- 76
- 主要终点
- Overall Survival (OS) at Primary Endpoint
研究概览
简要总结
The purpose of the study is to compare the clinical benefit, as measured by duration of overall survival, of Nivolumab vs. Everolimus in subjects with advanced or metastatic clear-cell renal cell carcinoma who have received prior anti-angiogenic therapy
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 & women ≥18 years of age
- •Histologic confirmation of renal cell carcinoma (RCC) with clear-cell component
- •Advanced/metastatic RCC
- •Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
- •Received 1 or 2 prior anti-angiogenic therapy regimens in advanced or metastatic setting
- •No more than 3 total prior systemic treatment regimens in the advanced or metastatic setting, and evidence of progression on or after last treatment regimen received and within 6 months of enrollment
- •Karnofsky Performance Score ≥70%
排除标准
- •Any Central Nervous System (CNS) metastases or history of CNS metastases
- •Prior therapy with an Mammalian target of rapamycin (mTOR) inhibitor
- •Any active known or suspected autoimmune disease
- •Uncontrolled adrenal insufficiency
- •Active chronic liver disease
- •Prior malignancy active within past 3 years, except for locally curable cancers
- •Other protocol-defined inclusion/exclusion criteria apply
研究组 & 干预措施
Arm 1: Nivolumab
Nivolumab 3 mg/kg solution intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
干预措施: Nivolumab (Biological)
Arm 2: Everolimus
Everolimus 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
干预措施: Everolimus (Drug)
结局指标
主要结局
Overall Survival (OS) at Primary Endpoint
时间窗: Randomization until 398 deaths, up to May 2015 (approximately 30 months)
Overall Survival (OS) was defined as the time from randomization to the date of death. Participants that had not died were censored at last known date alive. Median OS time was calculated using Kaplan-Meier Estimates. Interim analysis for the Primary Endpoint occurred after 398 deaths (70% of the total OS events needed for final analysis). At that time the data monitoring committee noted that the pre-specified boundary for OS (nominal significance level p \< 0.0148) was crossed while no new safety signals that would affect continuation of the study were found. The study was stopped early by the Sponsor, Bristol-Myers Squibb (BMS) and the interim analysis became the final analysis. As a result, participants in the everolimus groups could be assessed for a crossover to nivolumab treatment if they met all inclusion criteria.
次要结局
- Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events(Day of first dose to 30 days post study completion (approximately 106 months))
- Investigator-assessed Objective Response Rate (ORR)(from randomization up to disease progression or death (approximately up to 105 Months))
- Investigator-assessed Duration of Objective Response(From randomization to date of disease progression or death or censoring if no progression or death occurred (approximately 105 months))
- Number of Participants Meeting Marked Laboratory Abnormality Criteria in Specific Liver and Thyroid Tests(Day 1 to 30 days post study completion (approximately 106 months))
- Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units(Day 1 to 30 days post study completion (approximately 106 months))
- Investigator-assessed Time to Objective Response(Randomization to date of first response (approximately 105 months))
- Percentage of Participants With Disease-related Symptom Progression (DRSP)(from randomization up to disease progression or death (approximately up to 105 Months))
- Investigator-assessed Time of Progression-free Survival (PFS)(from randomization up to disease progression or death (approximately up to 105 Months))
- Overall Survival (OS) by Programmed Death-Ligand 1 (PD-L1) Expression Level(Randomization to date of death or date of last contact for patients without documentation of death, up to May 2015 (approximately 30 months))