Phase 1/2 Study of BMS-986310 Administered Alone and in Combination With Nivolumab in Participants With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 27
- 试验地点
- 5
- 主要终点
- Incidence of AEs meeting protocol-defined dose-limiting toxicity (DLT) criteria
研究概览
简要总结
The purpose of this study is to determine if BMS-986310 administered in combination with nivolumab, will demonstrate adequate safety and tolerability, as well as a favorable risk/benefit profile, to support further clinical testing.
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
- •Patients with measurable disease per RECIST v1.1 and have at least one lesion accessible for biopsy.
- •ECOG performance status less than or equal to 1
- •Part 1 and Sub-study B:
- •i) Part 1 participants must have advanced or metastatic disease where no other standard of care treatment option is possible.
- •ii) Sub-study B participants must have advanced or metastatic disease where no other standard of care treatment is possible, in one of the following tumor types: Renal cell carcinoma, Melanoma, colorectal cancer (CRC) microsatellite instability (MSI)-High (determined by Clinical Laboratory Improvement Amendments (CLIA) validated assay, testing methodology must be provided), Bladder cancer, Squamous Cell Carcinoma of the Head and Neck (SCCHN), and they must have had disease progression on an anti-PD-(L)1 based regimen as their most recent prior therapy
- •Sub-study A:
- •i) Participants must be newly diagnosed, no prior history of treatment for bladder cancer ii) Participants must not meet criteria for standard of care neoadjuvant therapy and must be candidates for SOC surgical resection of primary tumor.
- •iii) Histologically confirmed muscle-Invasive bladder cancer (MIBC) pure or mixed histology urothelial carcinoma Part 2 - Patients with relapsed / refractory solid tumors where no other standard of care treatment option is available.
排除标准
- •History of severe adverse drug reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) or Cyclooxygenase-2 (COX-2) inhibitors.
- •Participants with an active, known or suspected autoimmune disease.
- •Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations beyond what is consistent with the target population
研究组 & 干预措施
Dose Escalation
Part 1: BMS-986310 + Nivolumab Combination Dose Escalation
Sub-Study A: A cohort of Cisplatin Ineligible Muscle Invasive Bladder Cancer patients will receive either monotherapy BMS-986310, or BMS-986310 + Nivolumab, or Nivolumab monotherapy.
Sub-Study B: A cohort of PD[L]1 relapsed / refractory tumor cancer patients will be treated with monotherapy BMS-986310 followed by BMS-986310 + nivolumab
干预措施: BMS-986310 (Drug)
Dose Escalation
Part 1: BMS-986310 + Nivolumab Combination Dose Escalation
Sub-Study A: A cohort of Cisplatin Ineligible Muscle Invasive Bladder Cancer patients will receive either monotherapy BMS-986310, or BMS-986310 + Nivolumab, or Nivolumab monotherapy.
Sub-Study B: A cohort of PD[L]1 relapsed / refractory tumor cancer patients will be treated with monotherapy BMS-986310 followed by BMS-986310 + nivolumab
干预措施: Nivolumab (Biological)
Cohort Expansion
Part 2: Cohort Expansion will initiate upon consideration of the totality of data from Part 1.
BMS-986310 + Nivolumab combination will be administered in specific patient populations.
干预措施: BMS-986310 (Drug)
Cohort Expansion
Part 2: Cohort Expansion will initiate upon consideration of the totality of data from Part 1.
BMS-986310 + Nivolumab combination will be administered in specific patient populations.
干预措施: Nivolumab (Biological)
结局指标
主要结局
Incidence of AEs meeting protocol-defined dose-limiting toxicity (DLT) criteria
时间窗: up to 3 years
Incidence of Serious Adverse Events (SAE)
时间窗: up to 3 years
Incidence of death
时间窗: up to 3 years
Incidence of Adverse Events (AE)
时间窗: up to 3 years
Incidence of AEs leading to dose delays and discontinuation or delay in radical cystectomy (RC)
时间窗: up to 3 years
Incidence of Laboratory abnormalities
时间窗: up to 3 years
次要结局
- Progression free survival rate (PFSR)(up to 24 months)
- Observed serum concentration at the end of a dosing interval (Ctau)(up to 3 years)
- Area under the serum concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)](up to 3 years)
- Apparent total body clearance (CLT/F)(up to 3 years)
- Area under the serum concentration-time curve in 1 dosing interval [AUC(TAU)](up to 3 years)
- Summary changes of prostaglandin E metabolite (PGEM) in urine(up to 3 years)
- AUC accumulation index (AI_AUC)(up to 3 years)
- Summary changes of tumor necrosis factor (TNFa) in blood(up to 3 years)
- Objective response rate (ORR)(up to 3 years)
- Median duration of response (mDOR)(up to 3 years)
- Maximum observed serum concentration (Cmax)(up to 3 years)
- Summary of PK parameters at T-HALF(up to 3 years)
- Summary of PK parameter AUC(INF) after single dose(up to 3 years)
- Cmax accumulation index (AI_Cmax)(up to 3 years)