A Phase 1/2 Dose Escalation and Combination Cohort Study to Evaluate the Safety and Tolerability, Pharmacokinetics, and Efficacy of BMS-986226 Alone or in Combination With Nivolumab or Ipilimumab in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 80
- 试验地点
- 13
- 主要终点
- The Number of Participants Experiencing Adverse Events (AEs)
研究概览
简要总结
The purpose of this study is to investigate BMS-986226 administered alone or in combination with nivolumab or ipilimumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Advanced solid tumors
- •Histological or cytological confirmation of a malignancy that is advanced (metastatic and/or unresectable) with measureable disease as defined by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 or PCWG3 (prostate only).
- •At least 1 lesion accessible for biopsy in addition to the target lesion
- •Participants must have received, and then progressed or been intolerant to, at least 1 standard treatment regimen
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤2
排除标准
- •Participants with active central nervous system (CNS) metastases, untreated CNS metastases, or with the CNS as the only site of disease are excluded (controlled brain metastases will be allowed to enroll)
- •Participants with carcinomatous meningitis
- •Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast
- •Active, known, or suspected autoimmune disease
- •Uncontrolled or significant cardiovascular disease
- •Participants with known allergies to egg products, neomycin and tetanus toxoid.
- •Prior adverse reaction to tetanus toxoid- containing vaccines.
- •Other protocol defined inclusion/exclusion criteria could apply
研究组 & 干预措施
BMS-986226
administered intravenously
干预措施: BMS-986226 (Drug)
BMS-986226
administered intravenously
干预措施: Tetanus Vaccine (Biological)
BMS-986226 and Nivolumab
administered intravenously
干预措施: BMS-986226 (Drug)
BMS-986226 and Nivolumab
administered intravenously
干预措施: Nivolumab (Biological)
BMS-986226 and Nivolumab
administered intravenously
干预措施: Tetanus Vaccine (Biological)
BMS-986226 and Ipilimumab
administered intravenously
干预措施: BMS-986226 (Drug)
BMS-986226 and Ipilimumab
administered intravenously
干预措施: Ipilimumab (Biological)
BMS-986226 and Ipilimumab
administered intravenously
干预措施: Tetanus Vaccine (Biological)
结局指标
主要结局
The Number of Participants Experiencing Adverse Events (AEs)
时间窗: From first dose up to 100 days post last dose, up to approximately 31 months
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
The Number of Participants Experiencing Serious Adverse Events (SAEs)
时间窗: From first dose up to 100 days post last dose, up to approximately 31 months
Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or causes prolongation of existing hospitalization.
The Number of Participants Experiencing Adverse Events (AEs) Meeting Dose Limiting Toxicity (DLT) Criteria
时间窗: From first dose up to 100 days post last dose, up to approximately 31 months
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Dose limiting toxicity (DLT) is defined based on the incidence, intensity, and duration of AEs for which no clear alternative cause is identified. The DLT period will be 28 days (4 weeks) in the Preliminary Safety Cohorts. Any toxicities that occur beyond the 4-week DLT period will also be considered in dose-level decisions. For the purpose of participant management, any AE that meets DLT criteria, regardless of the cycle in which it occurs, will lead to discontinuation of study treatment. AEs will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03.
The Number of Participants Experiencing Adverse Events Leading to Discontinuation
时间窗: From first dose up to 100 days post last dose, up to approximately 31 months
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
The Number of Participants Experiencing Adverse Events Resulting in Death
时间窗: From first dose up to 100 days post last dose, up to approximately 31 months
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
The Number of Participants Experiencing Clinical Laboratory Abnormalities
时间窗: From first dose up to 30 days post last dose (approximately 28 months)
The number of participants experiencing abnormal laboratory results of Grade 3 or higher. Laboratory values will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 with Grade 3=severe and Grade 4=life threatening.
次要结局
- Objective Response Rate (ORR)(From first dose up to documented disease progression, up to 48 months)
- Median Duration of Response (DOR)(From first dose up to the date of the first objectively documented tumor progression or death, whichever occurs first (up to approximately 24 months))
- Progression Free Survival (PFS) Rate at 24 Weeks(At 24 weeks)
- Number of Participants With Anti-Drug Antibodies (ADA) for BMS-986226(Predose on cycles 1-6, post dose on C1D15, and 30, 60, and 100 days post last dose (up to approximately 31 months))
- Changes From Baseline in Cell Surface ICOS Expression on T Cells(From baseline up to pre-dose and 4 hours post dose on C1D1 and pre-dose and 4 hours post dose on C2D1 (approximately 31 months))
- Changes From Baseline in ICOS Ligand+ B Cells(From baseline up to pre-dose and 4 hours post dose on C1D1, 72 hours post dose on C1D4, and pre-dose on C2D1 (approximately 31 months))
- Maximum Observed Plasma Concentration (Cmax)(Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1, and C3D1 (approximately 31 months))
- Effective Elimination Half-Life (T-HALFeff)(Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C2D1 and C3D1 (approximately 31 months))
- Trough Observed Serum Concentrations (Ctrough)(Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C2D1 and C3D1. Pre-dose and 0.5 post dose on C4D1. Pre-dose on C5D1 and C6D1. Pre-dose and 0.5 hours post dose on C7D1. (approximately 31 months))
- Time of Maximum Observed Serum Concentration (Tmax)(Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1, and C3D1 (approximately 31 months))
- Area Under Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration [AUC (0-T)](Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1, and C3D1 (approximately 31 months))
- Area Under the Concentration-Time Curve in 1 Dosing Interval [AUC (TAU)](Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1, and C3D1 (approximately 31 months))
- Total Body Clearance (CLT)(Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1, and C3D1 (approximately 31 months))
- Average Concentration Over a Dosing Interval (Css-avg)(Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1, and C3D1 (approximately 31 months))
- Accumulation Index - Area Under Curve (AI-AUC)(Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1, and C3D1 (approximately 31 months))
- Accumulation Index - Cmax (AI-Cmax)(Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1 and C3D1. Pre-dose and 0.5 post dose on C4D1. (Approximately 31 months))
- Accumulation Index - Concentrations at the End of Dosing Interval (AI-CTAU)(Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1 and C3D1. Pre-dose and 0.5 post dose on C4D1. (Approximately 31 months))