An Exploratory Study to Investigate the Immunomodulatory Activity of Various Dose Levels of Anti Programmed-Death-1 (PD-1) Antibody (BMS-936558) in Subjects With Metastatic Clear Cell Renal Cell Carcinoma (RCC).
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 119
- 试验地点
- 13
- 主要终点
- Mean Serum Cytokines: CXCL9
研究概览
简要总结
The purpose of this study is to evaluate the pharmacodynamic and biologic properties of BMS-936558 in subjects with metastatic renal cell carcinoma.
详细描述
Intervention Model: Parallel Dose Comparison
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 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
- •Women and men ≥ 18 years of age.
- •Histologic confirmation of renal cell carcinoma with a clear cell component.
- •Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST).
- •Tumor sites that can be accessed for repeat biopsies at acceptable clinical risk.
- •Previously treated subjects must have failed at least 1 prior anti-angiogenic agent and can have a maximum of 3 prior systemic treatments for renal cell cancer.
- •Subjects in the treatment naive arm cannot have received prior systemic therapy for their renal cell carcinoma.
排除标准
- •Active or progressing brain metastases.
- •Active concomitant.
- •Active or history of autoimmune disease.
- •Active use of systemic corticosteroids.
- •Prior therapy with Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA4), anti Programmed death-1 (anti-PD1), anti Programmed death ligand 1 (anti-PD-L1), anti Programmed death ligand 2 (anti-PD-L2), anti-CD137, anti-CD40, anti-OX40 antibodies.
研究组 & 干预措施
Arm 1: BMS-936558
干预措施: BMS-936558 (Anti-PD-1) (Drug)
Arm 2: BMS-936558
干预措施: BMS-936558 (Anti-PD-1) (Drug)
Arm 3: BMS-936558
干预措施: BMS-936558 (Anti-PD-1) (Drug)
Arm 4: BMS-936558
(treatment naive)
干预措施: BMS-936558 (Anti-PD-1) (Drug)
结局指标
主要结局
Mean Serum Cytokines: CXCL9
时间窗: Baseline, Cycle 1 Day 1 3 Hrs Post, Cycle 1 Day 1 7 Hr Post, Cycle 1 Day 2 24 Hr Post, Cycle 2 Day 1 0 Hr Pre, Cycle 2 Day 8 168 Hrs Post, Cycle 4 Day 1 O Hr Pre (~39 months)
Objective is to investigate the pharmacodynamic immunomodulatory activity of serum chemokines (CXCL9, CXCL10)
Mean Serum Cytokines CXCL10 (IP10)
时间窗: Baseline, Cycle 1 Day 1 3 Hrs Post, Cycle 1 Day 1 7 Hr Post, Cycle 1 Day 2 24 Hr Post, Cycle 2 Day 1 0 Hr Pre, Cycle 2 Day 8 168 Hrs Post, Cycle 4 Day 1 O Hr Pre (~39 months)
Objective is to investigate the pharmacodynamic immunomodulatory activity of serum chemokines (CXCL9, CXCL10)
Percent Change From Baseline in Activated and Memory T Cells
时间窗: Baseline, Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 2 Day 8, Cycle 4 Day 1
The objective of the study was to investigate the pharmacodynamic immunomodulatory activity of anti-PD-1 antibody in activated and memory T cells with metastatic clear-cell Renal Cell Carcinoma (RCC)
Mean CD4 T Cell Infiltration
时间窗: Cycle 2 Day 8 168 Hr post dose
The objective of the study was to investigate the pharmacodynamic immunomodulatory activity of anti-PD-1 antibody on circulating CD4 infiltrations in tumors in participants with metastatic clear-cell Renal Cell Carcinoma (RCC).
Mean CD8 T Cell Infiltration
时间窗: 168 hour post does Cycle 2 Day 8 in evaluable participates (First active dose of study medication to cycle two day eight post injection)
The objective of the study was to investigate the pharmacodynamic immunomodulatory activity of anti-PD-1 antibody on circulating CD8 infiltrations in tumors in participants with metastatic clear-cell Renal Cell Carcinoma (RCC).
次要结局
- Best Overall Response in the BMS-936558 Arms(Assessed at a minimum of every 3 weeks up to 70 days following discontinuation of study drug (up to approximately 39 months))
- Immunogenicity of BMS-936558 as Measured by the Detection of Human Antibodies Against BMS-936558(Pre-dose, Cycle 4 Day 1, Cycle 8 Day 1 and during follow-up.)
- Progression Free Survival Rate in BMS-936558(Progression free survival rate will be assessed in each individual treatment arm by tumor assessments at 16, 24, and 48 weeks. From initial dose to end of study (assessed up to 39 months))
- Objective Response Rate in BMS-936558(Up to 22 months after study start)
- Duration of Objective Response for BMS-936558(The time when the measurement criteria are first met for PR or CR (whichever is reported first) until the date of documented disease progression or death (assessed up to 39 months))
- Duration of Stable Disease for BMS-936558 as Measured in Participants Whose Best Overall Response is Stable Disease as the Time From Baseline Until the Date of Documented Disease Progression or Death(The time from treatment arm assignment until the criteria for progression are met or death (whichever occurs first)(assessed up to 39 months))