A Multicenter, Open-Label, Phase 1 First in Human Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Intravenous MNK-010 in Subjects With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Mallinckrodt
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose (MTD)
研究概览
简要总结
This is a multicenter, open-label, dose escalation study of MNK-010 in subjects with advanced solid malignancies who have failed conventional therapy. The safety, tolerability, pharmacokinetic (PK) profile, and preliminary antitumor activity of ascending doses of MNK-010 will be evaluated in subjects with advanced solid tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Subject has received any chemotherapy, immunotherapy, vaccines, monoclonal antibodies, whether conventional or investigational, major surgery within 21 days, or radiotherapy within 21 days of treatment in this study, or at any time during the study.
- •Subject has an active, uncontrolled systemic infection considered opportunistic, life-threatening, or clinically significant at the time of treatment.
- •Subject has symptomatic or untreated central nervous system (CNS) metastases; any type of active seizure disorder; febrile neutropenia; ≥ Grade 2 peripheral neuropathy; peritoneal or pleural effusions requiring a tap more frequently than every 14 days; QT interval corrected (QTc) prolongation or a prior history of serious arrhythmias or significant abnormalities on screening ECG; previously experienced a severe reaction to a liposomal product or a taxane; received IV treatment for bacterial/fungal infection within 7 days of screening.
- •Subject has known significant cardiovascular disease or cerebrovascular accident within 3 months of enrollment, or within the timeframe as stipulated in the additional criteria outlined in the protocol.
- •Subject requires the use of the following concomitant treatments/procedures at any time, per protocol.
- •Subject requires either moderate or strong (if weak, 2 or more) inhibitors or inducers of Cytochrome P450 3A (CYP3A) mediated metabolism.
研究组 & 干预措施
MNK-010
Subjects will receive 1 dose of MNK-010 followed by a 7-day post dose assessment period per treatment cycle. Dose levels will be based upon the amount of active delivered per square meter of body surface area (mg/m2). Cycles will repeat every 3 weeks (21 days) based on toxicity and response, as determined by a Safety Review Committee (SRC). Subjects will continue treatment with MNK-010 until unacceptable toxicity, documented progression of disease, another criterion for discontinuation is met, or until 4 treatment cycles have been completed.
干预措施: MNK-010 (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD)
时间窗: 27 months
MTD of MNK-010
Treatment-emergent adverse events (TEAEs)
时间窗: 27 months
Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events (AEs) of at least Grade 3 severity, and discontinuations due to AEs. AEs will be evaluated and categorized in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events
Clinical labs
时间窗: 27 months
Changes from baseline in clinical laboratory assessments, vital signs, arterial oxygen saturation (SaO2) by pulse oximetry, physical examination, and 12-lead electrocardiograms (ECGs)
次要结局
- Plasma PK(27 months)
- Overall response(27 months)