Phase I/II Pharmacokinetic Multi-Tumor Study of Subcutaneous Formulation of Nivolumab Monotherapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 139
- 试验地点
- 36
- 主要终点
- Maximum Observed Serum Nivolumab Concentration (Cmax) - Parts A, B, D, and E
研究概览
简要总结
The purpose of this study is to investigate the effects of nivolumab when given under the skin with or without rHuPH20.
This study will include participants with 1 of the following advanced or metastatic tumors approved for treatment with nivolumab monotherapy:
- non-small cell lung cancer (NSCLC)
- renal cell carcinoma (RCC)
- unresectable or metastatic melanoma
- hepatocellular carcinoma (HCC)
- microsatellite instability-high or mismatch repair deficient colorectal cancer (MSI-H/dMMR CRC)
- in Part B, other solid tumors may be considered at the discretion of the Clinical Trial Physician
- In addition to the above tumors, Part E will also include participants with metastatic urothelial carcinoma (mUC).
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
- •Histologic or cytologic confirmation of advanced (metastatic and/or unresectable) solid tumors of one of the following tumor types:
- •Metastatic squamous or non-squamous NSCLC
- •RCC, advanced or metastatic
- •CRC, metastatic (MSI-H or dMMR)
- •In Part B, other solid tumor types may be considered at the discretion of the Medical Monitor
- •In Part E, Metastatic urothelial carcinoma
- •Measurable disease as per RECIST version 1.1 criteria
- •ECOG performance status of 0 or 1
排除标准
- •Active brain metastases or leptomeningeal metastases
- •Ocular melanoma
- •Active, known, or suspected autoimmune disease
- •Other protocol defined inclusion/exclusion criteria apply
研究组 & 干预措施
Part A, Group 1: nivolumab (dose 1) + rHuPH20
干预措施: nivolumab (Biological)
Part A, Group 1: nivolumab (dose 1) + rHuPH20
干预措施: rHuPH20 (Drug)
Part B, Group 3: nivolumab (dose 2) + rHuPH20
干预措施: nivolumab (Biological)
Part B, Group 3: nivolumab (dose 2) + rHuPH20
干预措施: rHuPH20 (Drug)
Part B, Group 2: nivolumab (dose 1)
干预措施: nivolumab (Biological)
Part B, Group 4: nivolumab (dose 2)
干预措施: nivolumab (Biological)
Part C: nivolumab (dose 3) + rHuPH20
干预措施: nivolumab (Biological)
Part C: nivolumab (dose 3) + rHuPH20
干预措施: rHuPH20 (Drug)
Part D, Group 5: nivolumab (dose 3) + rHuPH20
干预措施: nivolumab (Biological)
Part D, Group 5: nivolumab (dose 3) + rHuPH20
干预措施: rHuPH20 (Drug)
Part E, Group 6: nivolumab (dose 4) coformulated with rHuPH20
干预措施: nivolumab (Biological)
Part E, Group 6: nivolumab (dose 4) coformulated with rHuPH20
干预措施: rHuPH20 (Drug)
结局指标
主要结局
Maximum Observed Serum Nivolumab Concentration (Cmax) - Parts A, B, D, and E
时间窗: From first dose until approximately 21 days post first dose.
Cmax is the maximum observed serum nivolumab concentration. Collected for Arm A, B, and D on Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 4, Cycle 1 Day 8, Cycle 1 Day 15, and Cycle 1 Day 21. Collected for Arm E on Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 4, Cycle 1 Day 8, Cycle 1 Day 15.
Time Taken to Reach Cmax (Tmax) - Parts A, B, D, and E
时间窗: From first dose until approximately 21 days post first dose.
Tmax is the time taken to reach the maximum observed serum nivolumab concentration (Cmax). Collected for Arm A, B, and D on Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 4, Cycle 1 Day 8, Cycle 1 Day 15, and Cycle 1 Day 21. Collected for Arm E on Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 4, Cycle 1 Day 8, Cycle 1 Day 15.
Area Under the Time-Serum Nivolumab Concentration Curve (AUC (TAU)) - Parts A, B, D, and E
时间窗: From first dose until approximately 21 days post first dose.
AUC (TAU) is the area measured under the concentration-time curve taken over the dosing interval. Collected for Arm A, B, and D on Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 4, Cycle 1 Day 8, Cycle 1 Day 15, and Cycle 1 Day 21. Collected for Arm E on Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 4, Cycle 1 Day 8, Cycle 1 Day 15.
Observed Serum Nivolumab Concentration at the End of Dosing (Ctau) - Parts A, B, D, and E
时间窗: At the end of dosing interval of Cycle 1 - first dose (Day 21 for Parts A, B and D; Day 15 for Part E)
Ctau is the observed serum nivolumab concentration at the end of the dosing interval. Collected for Arma A, B, and D.
Lowest Observed Serum Nivolumab Concentration (Ctrough) During Part C - Part A and B Crossover Participants to Part C
时间窗: On Day 1 of Cycles 2, 3, 5, 9, 13, and 19 of Part C (Day 1 of Part C: up to 14 months from Baseline; each cycle was 28 days)
Ctrough assessed during Part C. Ctrough is the lowest observed serum nivolumab concentration.
次要结局
- Number of Participants Experiencing Adverse Events (AEs)(From first dose until 100 days post last dose (up to approximately 70 months).)
- Number of Participants Experiencing Treatment Related Adverse Events (TRAEs)(From first dose until 100 days post last dose (up to approximately 70 months).)
- Number of Participants Experiencing Serious Adverse Events (SAEs)(From first dose until 100 days post last dose (up to approximately 70 months).)
- Number of Participants Experiencing Treatment Related Serious Adverse Events (TRSAEs)(From first dose until 100 days post last dose (up to approximately 70 months).)
- Number of Participants Experiencing Treatment Related Adverse Events (TRAEs) Leading to Discontinuation(From first dose until 100 days post last dose (up to approximately 70 months).)
- Number of Participants Who Died(From randomization until data cutoff (up to approximately 70 months).)
- Number of Participants With Select Laboratory Changes From Baseline(From first dose until 30 days post last dose (up to approximately 67 months and 20 days).)
- Number of Participants Experiencing Any Select Adverse Events Within the Hypersensitivity/Infusion Reaction Category and Broad Standardized MedDRA Query (SMQ) of Anaphylactic Reaction Occurring Within 2 Days of Study Drug Administration(From first dose until 2 days post last dose (up to approximately 66 months and 22 days).)
- Number of Participants With Anti-Nivolumab Antibodies (ADAs) and Neutralizing Antibodies(At baseline and up to 100 days post last dose (up to approximately 70 months).)