A Phase I/IIa Study of BMS-986148, a Mesothelin Directed Antibody Drug Conjugate, in Subjects With Select Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 126
- 试验地点
- 17
- 主要终点
- Number of Participants With Adverse Events at Worst CTC Grade
研究概览
简要总结
The purpose of this study is to determine the safety, tolerability, pharmacokinetics, immunogenicity, antitumor activity and pharmacodynamics of BMS-986148 administered alone and in combination with nivolumab in patients with mesothelioma, non-small cell lung cancer, ovarian cancer, pancreatic cancer and gastric cancer.
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
- •Must have pancreatic, ovarian, gastric, non-small cell cancer or mesothelioma. For dose expansion, must have tumor that is positive for mesothelin
- •Expected to have life expectancy of at least 3 months
- •Men and women 18 years old or older (or local age of majority)
- •Must have measurable tumor per Response Evaluation Criteria In Solid Tumors (RECIST) or modified RECIST for malignant pleural mesothelioma
- •ECOG of 0 to 1
排除标准
- •Cancer metastases in the brain
- •Moderate eye disorders
- •Active infection or past hepatitis B or C infection
- •Major surgery less than 1 month before the start of the study
- •Uncontrolled heart disease
- •Impaired liver or bone marrow function
- •History of allergy to mesothelin-directed antibodies, tubulysin, monoclonal antibodies, nivolumab or related compounds
研究组 & 干预措施
Part 1: Ascending dose of BMS-986148
BMS-986148 Intravenous injection at increasing doses on specific days until the maximum tolerated dose is reached. Five cancers will be studied in this part: mesothelioma, pancreatic, ovarian, gastric, and non-small cell lung cancer. Alternate dose and schedules may be explored.
干预措施: BMS-986148 (Drug)
Part 2: Expansion dose of BMS-986148
BMS-986148 Intravenous injection of Maximum tolerated dose (MTD) on specific days. Five cancers will be studied in this part: mesothelioma, pancreatic, ovarian, gastric, and non-small cell lung cancer.
干预措施: BMS-986148 (Drug)
Part 3A: Ascending dose of BMS-986148
Set dose of nivolumab and BMS-986148 intravenous injection at increasing doses on specific days until the maximum tolerated dose is reached. Five cancers will be studied in this part: mesothelioma, pancreatic, ovarian, gastric, and non-small cell lung cancer.
干预措施: BMS-986148 (Drug)
Part 3A: Ascending dose of BMS-986148
Set dose of nivolumab and BMS-986148 intravenous injection at increasing doses on specific days until the maximum tolerated dose is reached. Five cancers will be studied in this part: mesothelioma, pancreatic, ovarian, gastric, and non-small cell lung cancer.
干预措施: Nivolumab (Biological)
Part 3B: Expansion dose of BMS-986148
Set dose of nivolumab and BMS-986148 intravenous injection at or below maximum tolerated dose on specific days. Five cancers will be studied in this part: mesothelioma, pancreatic, ovarian, gastric, and non-small cell lung cancer.
干预措施: BMS-986148 (Drug)
Part 3B: Expansion dose of BMS-986148
Set dose of nivolumab and BMS-986148 intravenous injection at or below maximum tolerated dose on specific days. Five cancers will be studied in this part: mesothelioma, pancreatic, ovarian, gastric, and non-small cell lung cancer.
干预措施: Nivolumab (Biological)
结局指标
主要结局
Number of Participants With Adverse Events at Worst CTC Grade
时间窗: From first dose to up to 100 days post last dose (Up to 6 months)
Number of participants with adverse events at worst CTC grade including any grade adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuations, and deaths grouped by dose + dose regimen.
Number of Participants With Laboratory Test Toxicity Grade Shifting From Baseline
时间窗: From first dose to up to 100 days post last dose (Up to 6 months)
Number of participants with laboratory test toxicity grade (Grade 0, 1, 2, 3, and 4) in hematology and chemistry shifting from baseline. An increase in baseline indicates a shift of participant to a greater toxicity grade. A decrease in baseline indicates a shift of participant to a lesser toxicity grade. Participants are grouped by dose + dose regimen assessed by NCT CTCAE V 4.03.
次要结局
- Progression Free Survival Rate (PFSR) at Week t(Total PFS assessed between 4 and 12 months, PFSR at months 4 and 6 to be reported)
- Changes in QT Corrected by the Fridericia Formula (QTcF) From Baseline, at Selected Times(Up to 58 months)
- Number of Participants With Anti-Drug Antibody (ADA)(Up to 58 months)
- Maximum Observed Serum Concentration (Cmax)(PK blood assessed on cycle 1, day 1)
- Time of Maximum Observed Serum Concentration (Tmax)(PK blood assessed on cycle 1, day 1)
- Concentration at the End of a Dosing Interval (Ctau)(PK blood assessed on cycle 1, day 1)
- Trough Observed Serum Concentration (Ctrough)(PK blood assessment include cycle 2-day 1 and cycle 1-day 8)
- Area Under the Concentration-Time Curve From Time Zero to Time T (AUC(0-t))(PK blood assessment include cycle 1-day 1)
- Area Under the Concentration-Time Curve in One Dosing Interval (AUC[TAU])(PK blood assessment include cycle 1-day 1)
- Best Overall Response (BOR)(Up to 58 months)
- Objective Response Rate (ORR)(Up to 58 months)
- Duration of Response (DoR)(Up to 58 months)
- Progression Free Survival (PFS)(Up to 58 months)