A Phase 1 First-In-Human Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of AMG 673 Administered as Short Term Intravenous Infusions in Subjects With Relapsed/Refractory Acute Myeloid Leukemia
试验速览
- 阶段
- 早期 1 期
- 状态
- 终止
- 发起方
- Amgen
- 入组人数
- 46
- 试验地点
- 7
- 主要终点
- Number of Participants With Treatment-emergent Adverse Events
研究概览
简要总结
The primary objectives of this study are to evaluate the safety and tolerability of emerfetamab in adults with relapsed/refractory acute myeloid leukemia (AML) and to estimate the maximum tolerated dose (MTD) and/or a biologically active dose (eg, recommended phase 2 dose [RP2D]).
详细描述
This is a first-in-human, open-label, phase 1, sequential dose escalation study. Emerfetamab will be evaluated as a short term intravenous (IV) infusion in adults with relapsed/refractory AML The study will consist of a dose escalation phase and a dose expansion phase. The study was terminated prior to the start of the expansion phase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Dose Escalation
The dose-escalation cohorts to estimate the MTD will use 2 schedules of emerfetamab administration: Schedule A (Day 1/Day 5 dosing in 14-day cycles) and Schedule B (once daily dosing for cycle 1 followed by twice weekly dosing in following cycles).
For Schedule A the starting dose for the first cohort will be 0.05 μg emerfetamab administered as short term IV infusions on day 1 and day 5. The doses administered for the following cohorts will be recommended by the Dose Level Review Team (DLRT).
For Schedule B the starting dose will be 72 μg emerfetamab administered as short-term IV infusions daily (QD) during the 14-day cycle 1 after the 72 μg target dose is found to be relatively safe and tolerable by the DLRT for Schedule A.
干预措施: Emerfetamab (Drug)
Expansion Phase
For each schedule, upon completion of the dose escalation cohorts, additional participants may be enrolled to receive emerfetamab at a dose at or below the MTD estimated in the dose escalation cohorts.
干预措施: Emerfetamab (Drug)
结局指标
主要结局
Number of Participants With Treatment-emergent Adverse Events
时间窗: From first dose of study drug until the end of study; median (minimum, maximum) duration was 1.22 (0.10, 5.98) months.
The severity of each adverse event (AE) was graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria, where Grade 1 = mild AE, Grade 2 = moderate AE, Grade 3 = severe AE, Grade 4 = life-threatening and Grade 5 = death due to AE. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria: * fatal * life threatening * required in patient hospitalization or prolongation of existing hospitalization * resulted in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event.
Number of Participants With Dose-limiting Toxicities (DLT)
时间窗: Schedule A: From the start of the first infusion on day 1 until day 14. Schedule B: From the start of the first infusion on day 1 to day 28.
A DLT was defined as any of the events described below occurring in a participant during the DLT window, unless clearly attributable to causes other than emerfetamab: * Any treatment-related death; * Grade 4 neutropenia persisting at 42 days after the last infusion in treatment cycle 1; * Grade 3-5 non-hematologic toxicity not clearly resulting from the underlying leukemia with a few protocol-specified exceptions; * Grade 2 or 3 cytokine release syndrome (CRS) meeting any of the criteria listed below: * Grade 2 CRS that does not resolve, with or without intervention to Grade 1 within 7 days; * Grade 3 CRS that does not resolve, with or without intervention to Grade 2 within 5 days, or grade 1 within 7 days; * Grade 3 CRS reported at the initial dose; * Two separate grade 3 CRS events; * Grade 4 CRS occurring during treatment.
次要结局
- Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab(Cycle 1 day 1 at predose and at 1, 6, 24, and 48 hours after the start of infusion, and day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion.)
- Schedule B: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab(Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion.)
- Schedule B: Time to Maximum Observed Concentration (Tmax) of Emerfetamab(Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion.)
- Schedule B: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab(Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion.)
- Duration of Response(Disease response was assessed on day 14 of every treatment cycle and at the end of study; median (min, max) duration was 1.22 (0.10, 5.98) months.)
- Time to Response(Disease response was assessed on day 14 of every treatment cycle and at the end of study; median (min, max) duration was 1.22 (0.10, 5.98) months.)
- Time to Progression(Disease response was assessed on day 14 of every treatment cycle and at the end of study; median (min, max) duration was 1.22 (0.10, 5.98) months.)
- Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab(Cycle 1 day 1 at predose and at 1, 6, 24, and 48 hours after the start of infusion, and day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion.)
- Schedule A: Area Under the Concentration-time Curve From Time Zero to 96 Hours Post-dose (AUC0-96) on Day 1 for Emerfetamab(Cycle 1 day 1 at predose and at 1, 6, 24, 48, and 96 hours after the start of infusion.)
- Schedule A: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab(Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion.)
- Schedule A: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab(Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion.)
- Schedule A: AUC Total for Emerfetamab(Cycle 1 day 1 at predose and at 1, 6, 24, and 48 hours after the start of infusion, and day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion.)
- Schedule A: Terminal Half-life (T1/2,z) of Emerfetamab(Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion.)
- Schedule A: Clearance (CL) of Emerfetamab(Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion.)
- Schedule B: Maximum Observed Concentration (Cmax) of Emerfetamab(Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion.)
- Schedule B: Clearance of Emerfetamab(Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion.)
- Schedule B: Terminal Half-life (T1/2,z) of Emerfetamab(Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion.)
- Response Rate(Disease response was assessed on day 14 of every treatment cycle and at the end of study; median (min, max) duration was 1.22 (0.10, 5.98) months.)