A Phase 1/2 First-in-Human Study of BMS-986258 Alone and in Combination With Nivolumab in Advanced Malignant Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 92
- 试验地点
- 16
- 主要终点
- Number of Participants With Adverse Events (AEs)
研究概览
简要总结
The purpose of this study is to determine whether BMS-986258 both monotherapy and in combination with Nivolumab is safe and tolerable in the treatment of advanced malignant tumors.
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
- •Histologic confirmation of one of the 5 tumors [renal cell carcinoma (RCC), colorectal cancer (CRC), non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), triple negative breast cancer (TNBC)] (metastatic, recurrent, and/or unresectable), with measurable disease per response evaluation criteria in solid tumors v1.1 (RECIST v1.1)
- •Eastern Cooperative Oncology Group Performance Status of 0 or 1
- •Participants must have received, and then progressed, relapsed, or been intolerant to, at least 1 standard treatment regimen in the advanced or metastatic setting according to solid tumor histologies
- •Women must agree to follow specific methods of contraception, if applicable
排除标准
- •Active, known or suspected autoimmune disease
- •Cytotoxic agents, unless at least 4 weeks have elapsed from last dose of prior anti-cancer therapy and initiation of study therapy
- •Other active malignancy requiring concurrent intervention
- •Other protocol-defined inclusion/exclusion criteria apply
研究组 & 干预措施
Part C Cohort Expansion: BMS-986258 + nivolumab
干预措施: BMS-986258 (Biological)
Part C Cohort Expansion: BMS-986258 + nivolumab
干预措施: Nivolumab (Biological)
Part A Dose Escalation: BMS-986258
干预措施: BMS-986258 (Biological)
Part A1: BMS-986258 + Recombinant human hyaluronidase PH20 (rHuPH20)
干预措施: BMS-986258 (Biological)
Part A1: BMS-986258 + Recombinant human hyaluronidase PH20 (rHuPH20)
干预措施: rHuPH20 (Drug)
Part B Dose Escalation: BMS-986258 + nivolumab
干预措施: BMS-986258 (Biological)
Part B Dose Escalation: BMS-986258 + nivolumab
干预措施: Nivolumab (Biological)
结局指标
主要结局
Number of Participants With Adverse Events (AEs)
时间窗: From first dose until 100 days after last dose of study therapy (up to approximately 78 weeks)
An Adverse Event (AE) is any new untoward medical occurrence or worsening of a preexisting medical condition in a study participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. A Serious Adverse Event (SAE) is 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) * Requires inpatient hospitalization or causes prolongation of existing hospitalization * Results in persistent or significant disability/incapacity * Is a congenital anomaly/birth defect.
Number of Participants Who Died During the Study
时间窗: From first dose until death due to any cause (up to approximately 78 months)
The number of participants who died during the study.
Number of Participants With Dose Limiting Toxicities (DLTs)
时间窗: From first dose (Cycle 1 Day 1) until day 28 (Cycle 1 Day 28)
Dose-limiting toxicity (DLT) refers to a side effect or adverse reaction caused by a drug that is severe enough to prevent an increase in dose or level of that drug. It is typically identified during clinical trials to determine the highest dose of a drug that can be given safely without causing unacceptable side effects. A participant was considered DLT evaluable if they received 1 dose of BMS-986258 in Part A or 1 dose of BMS-986258 and nivolumab 480mg in Part B and completed the DLT observation period. Participants who withdraw from the study during the 4-week DLT evaluation period for reasons other than a DLT may be replaced with a new participant at the same dose level.
次要结局
- Objective Response Rate (ORR)(From first dose until disease progression or death, whichever occurred first (up to approximately 78 months))
- Median Duration of Response (mDOR)(From first dose until disease progression or death whichever occurred first (up to approximately 78 months))
- Progression-Free Survival (PFS) Rate at 6, 9, and 12 Months(At 6, 9, and 12 months after first dose)
- Maximum Plasma Concentration (Cmax) of BMS-986258(Part A and B: On Cycle 1 Day 1 and Cycle 3 Day 1 (1 cycle = 8 weeks); Part A1: On Cycle 1 Day 1 and Cycle 1 Day 29 (1 cycle = 8 weeks))
- Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258(Part A and B: On Cycle 1 Day 1 and Cycle 3 Day 1 (1 cycle = 8 weeks); Part A1: On Cycle 1 Day 1 and Cycle 1 Day 29 (1 cycle = 8 weeks))
- Area Under the Curve Over the Dosing Interval AUC(TAU) of BMS-986258(Part A and B: 0 to 28 days post-dose on Cycle 1 Day 1 and Cycle 3 Day 1 (1 cycle = 8 weeks); Part A1: 0 to 28 days post-dose on Cycle 1 Day 1 and Cycle 1 Day 29 (1 cycle = 8 weeks))
- Concentration at the End of the Dosing Interval (Ctau) of BMS-986258(Part A and B: On Cycle 1 Day 29 and Cycle 3 Day 29 (1 cycle = 8 weeks); Part A1: On Cycle 1 Day 29 and Cycle 2 Day 1 predose (1 cycle = 8 weeks))
- Time to Reach Maximum Concentration (Tmax) of BMS-986258(Part A and B: On Cycle 1 Day 1 and Cycle 3 Day 1 (1 cycle = 8 weeks); Part A1: On Cycle 1 Day 1 and Cycle 1 Day 29 (1 cycle = 8 weeks))
- Number of Participants With Anti-Drug Antibodies to BMS-986258 or Nivolumab(From first dose until 100 days after last dose of study therapy (up to approximately 78 weeks))