A Phase 1, Open-Label, Multicenter, Dose Escalation Study to Assess the Safety and Tolerability of MLN7243, an Inhibitor of Ubiquitin-Activating Enzyme (UAE), in Adult Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 29
- 主要终点
- Number of Participants With Vital Sign Related TEAEs by Preferred Term (PT)
研究概览
简要总结
The purpose of this study is to evaluate safety and tolerability (establish maximum tolerated dose [MTD], inform the recommended phase 2 dose [RP2D], and identify the dose-limiting toxicities [DLTs]) of MLN7243.
详细描述
This is a single arm Phase I study with multiple dosing cohorts as noted below:
- Schedule A: MLN7243 1 mg
- Schedule A: MLN7243 2 mg
- Schedule A: MLN7243 4 mg
- Schedule A: MLN7243 8 mg
- Schedule A: MLN7243 12 mg
- Schedule A: MLN7243 18 mg
- Schedule A: MLN7243 Homozygous Mutant 4 mg
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
Schedule A: MLN7243 1 mg
MLN7243 1 milligram (mg), infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or disease progression (PD) or discontinuation of study for another reason, or until study is stopped.
干预措施: MLN7243 (Drug)
Schedule A: MLN7243 2 mg
MLN7243 2 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD, or discontinuation of study for another reason, or until study is stopped.
干预措施: MLN7243 (Drug)
Schedule A: MLN7243 4 mg
MLN7243 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
干预措施: MLN7243 (Drug)
Schedule A: MLN7243 8 mg
MLN7243 8 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
干预措施: MLN7243 (Drug)
Schedule A: MLN7243 12 mg
MLN7243 12 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
干预措施: MLN7243 (Drug)
Schedule A: MLN7243 18 mg
MLN7243 18 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
干预措施: MLN7243 (Drug)
Schedule A: MLN7243 Homozygous Mutant 4 mg
MLN7243 homozygous mutant 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.
干预措施: MLN7243 (Drug)
结局指标
主要结局
Number of Participants With Vital Sign Related TEAEs by Preferred Term (PT)
时间窗: Baseline up to 30 days after last dose of study drug (Cycle 10 Day 41)
Number of Participants With Laboratory Related TEAEs by System Organ Class (SOC)
时间窗: Baseline up to 30 days after last dose of study drug (Cycle 10 Day 41)
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
时间窗: Cycle 1 Day 1 up to Cycle 1 Day 11
Number of Participants With Clinically Significant Echocardiogram Abnormalities
时间窗: Cycle 1 Day 2 up to 30 days after last dose of study drug (Cycle 10 Day 41)
Number of Participants With TEAEs Related to Tropinin I and T
时间窗: Baseline up to 30 days after last dose of study drug (Cycle 10 Day 41)
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
时间窗: Baseline up to 30 days after last dose of study drug (Cycle 10 Day 41)
次要结局
- CL: Total Clearance After Intravenous Administration for TAK-243(Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose)
- Change From Baseline in Immunohistochemistry (IHC) Biomarkers in Tumor Biopsies at Cycle 1 Day 12 (C1D12) as Assessed by Histological Score (H-score)(Baseline and Cycle 1 Day 12)
- Change From Baseline in IHC Biomarkers in Tumor Biopsies at C1D12 as Assessed by Positive Index(Baseline and Cycle 1 Day 12)
- Duration of Response(Baseline up to end of study (approximately 7 months))
- AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-243(Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose)
- Aet: Amount of TAK-243 Excreted Unchanged in Urine(Cycle 1 Day 1; Cycle 1 Day 11)
- AUCτ: Area Under the Plasma Concentration-time Curve Over the Dosing Interval for TAK-243(Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose)
- AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-243(Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose)
- Vss: Volume of Distribution at Steady State for TAK-243(Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose)
- Ceoi: Plasma Concentration at the End of Infusion for TAK-243(Cycle 1 Day 1 and 11: pre-infusion to end of infusion (up to 10 minutes))
- Fet: Percentage of TAK-243 Excreted Unchanged in Urine(Cycle 1 Day 1; Cycle 1 Day 11)
- Terminal Phase Elimination Half-life (T1/2) for TAK-243(Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose)
- Percentage of Participants With Best Overall Response(Baseline up to end of study (approximately 7 months))