An Open-Label, Randomized, Phase 2 Study of Nivolumab Given Sequentially With Ipilimumab in Subjects With Advanced or Metastatic Melanoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 138
- 试验地点
- 21
- 主要终点
- Percentage of Participants With Treatment-Related Grade 3-5 Adverse Events (AEs) During the Induction Period (Period 1 and 2)
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of a sequential combination therapy of Nivolumab and Ipilimumab
详细描述
In order to evaluate the potential synergistic activity of nivolumab and ipilimumab and also because there may be differences in biology between tumors which are stable or responding to therapy and those that are clinically progressing, this study, CA209064, looked at two sequential combination regimens in which the second agent is administered immediately after a pre-specified duration of therapy with the first agent and not delayed until the time of progression after the first agent. This sequential study design looked at pharmacodynamic changes during treatment with one agent which may predict clinical activity to subsequent treatment with the alternate agent. This was done because it has not been scientifically proven whether or not the order in which nivolumab and ipilimumab are given is clinically important.
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 confirmed unresectable Stage III or IV melanoma
- •Treatment-naive or experienced disease recurrence or progression during or after one prior systemic regimen for advanced disease
- •Measurable disease by Computed Tomography/Magnetic resonance imaging (CT/MRI) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Known BRAF V600 mutation status or consent to BRAF V600 mutation testing
- •Sufficient tumor tissue accessible for baseline and post-treatment biopsies.
排除标准
- •Active central nervous system (CNS) metastases
- •Carcinomatous meningitis
- •Active, known or suspected autoimmune disease
- •Condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization
- •Prior therapy with anti-Programmed Death-1 (PD1), anti-Programmed Death-Ligand 1 (PD-L1), anti-PD-L2, anti-CD137, or anti-CTLA-4 (cytotoxic T lymphocyte antigen 4) antibody
- •Prior treatment with other immunotherapies
- •Prior therapy with BRAF inhibitor within 6 weeks of enrollment
结局指标
主要结局
Percentage of Participants With Treatment-Related Grade 3-5 Adverse Events (AEs) During the Induction Period (Period 1 and 2)
时间窗: From Day 1 to up to Week 25
The percentage of participants with treatment-related grade 3-5 adverse events (AEs) is defined as the number of participants who experienced at least 1 treatment related grade 3 - 5 adverse event (AE) per national cancer institute common terminology criteria for adverse events (NCI CTCAE v4.0, any preferred term) with an onset date after or on first day of Induction Period #1 and not later than discontinuation date from Induction Period #2, divided by the total number of treated participants. Adverse Event (AE) = any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may or may not have a causal relationship with treatment. Treatment-related = having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 3=Severe Gr 4=Potentially Life-threatening or disabling Gr 5=Death
次要结局
- Investigator-Assessed Response Rate at Week 25(Week 25)
- Investigator-Assessed Duration of Response (DOR)(From week 25 to up to date of disease progression or death (Up to 6 years))
- Investigator-Assessed Rate of Progression(Week 13 and Week 25)