A Phase I/II, Dose-escalation and Dose-optimization Study to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of MT-4561 in Patients With Various Advanced Solid Tumors and to Evaluate Effect of MT-4561 on Pharmacokinetics of Oral Midazolam
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 27
- 试验地点
- 6
- 主要终点
- Incidence of Adverse Event, Dose limiting toxicities (DLTs)
研究概览
简要总结
This is a First In Human (FIH), multicenter, open-label, Phase I/II study to evaluate safety, tolerability, Pharmacokinetics (PK), pharmacodynamics, and efficacy of MT-4561 in patients with advanced solid tumors. This study will be conducted in 3 parts.
Part 1 is aimed at evaluating safety, tolerability, PK and pharmacodynamics of MT-4561 and determining the Maximum Tolerated Dose (MTD) using the Bayesian Optimal Interval (BOIN) design.
The study details and doses of Part 2 (dose-optimization) and Part 3 (Drug-Drug Interaction) will be available after review of applicable Part 1 results.
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
- •Patients who have failed at least 1 prior therapy and, who have no standard treatment options demonstrated to provide clinical benefit or who are intolerable to or refuse further standard therapies will be enrolled.
- •Male or female patient aged 18 years or older at the time of signing the informed consent form
- •≥ 1 measurable lesion by the RECIST v1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status: 0 to 1
- •Life expectancy of at least 3 months
- •Adequate bone marrow function
- •Adequate hepatic function
- •Adequate renal function estimated creatinine clearance ≥ 60 mL/min calculated using the Cockcroft and Gault equation or by institutional method
- •Part 1: Patients must have a confirmed histologic or cytologic diagnosis of one of the following solid tumors for participation in the study: head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), esophageal cancer, gastric cancer, biliary tract cancer, pancreatic ductal adenocarcinoma (PDAC), breast cancer, ovarian cancer, cervical cancer, endometrial cancer, prostate cancer, urothelial carcinoma, neuroendocrine tumor (NET) or neuroendocrine carcinoma (NEC), soft tissue sarcoma, and NUT carcinoma.
排除标准
- •Patients with active brain or leptomeningeal metastases
- •Any unresolved toxicity ≥ Grade 2 from previous anticancer therapy except for alopecia
- •Prior systemic anticancer therapy within 4 weeks before first dose of investigational medicinal product (IMP) or 5 half-lives, whichever is shorter, and prior radiotherapy within 2 weeks before first dose of IMP
- •History of congenital long QT syndrome or clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation or Torsades de pointes)
- •Patients who received drugs with a known risk of QT interval prolongation or Torsades de pointes within 14 days or 5 half-lives, whichever is shorter, before the start of IMP administration
- •QT interval corrected for heart rate using Fridericia's correction (QTcF) > 470 msec at screening
研究组 & 干预措施
Part 1 (Dose-escalation)
Intravenous (IV) infusion of MT-4561 once every week in 28-day cycle, until disease progression or discontinuation criteria are met.
干预措施: MT-4561 (Drug)
结局指标
主要结局
Incidence of Adverse Event, Dose limiting toxicities (DLTs)
时间窗: a 28-day cycle
Part 1 Frequency, duration, and severity (Common Terminology Criteria for Adverse Events \[CTCAE\] v5.0) of adverse events, dose limiting toxicity (DLT), physical examinations, changes in clinical laboratory values (e.g., hematology, chemistry, and urinalysis), vital signs (e.g., heart rate, blood pressure, respiratory rate), electrocardiogram DLTs are defined as any event meeting the DLT criteria at least possibly related to MT-4561 for Cycle 1 (i.e., DLT monitoring window is approximately 28 days). Events with a clear alternative explanation will not be considered DLTs.
Number of Patients with Adverse events (AEs)
时间窗: Screening through 30 days after last dose
Part 1 Frequency, duration, and severity (Common Terminology Criteria for Adverse Events \[CTCAE\] v5.0) of adverse events, dose limiting toxicity (DLT), physical examinations, changes in clinical laboratory values (e.g., hematology, chemistry, and urinalysis), vital signs (e.g., heart rate, blood pressure, respiratory rate), electrocardiogram Adverse event: An AE is defined as any untoward medical occurrence in a clinical study patient administered a pharmaceutical product, and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of an IMP, whether it is considered related to the IMP.
次要结局
- Cmax of MT-4561(Cycle 1 Day 1 through Cycle 2 Day 22 (each cycle is 28 days))
- time corresponding to occurrence of Cmax (tmax)(Cycle 1 Day 1 through Cycle 2 Day 22 (each cycle is 28 days))
- minimum observed plasma concentration (Cmin)(Cycle 1 Day 1 through Cycle 2 Day 22 (each cycle is 28 days))
- area under the concentration-time curve from zero up to 168 hours post-dose (AUC0-168)(Cycle 1 Day 1 through Cycle 2 Day 22 (each cycle is 28 days))
- Renal clearance (CL) after the first dose and at steady state(Cycle 1 Day 1 through Cycle 2 Day 22 (each cycle is 28 days))
- dose proportionality(Cycle 1 Day 1 through Cycle 2 Day 22 (each cycle is 28 days))
- accumulation ratio(Cycle 1 Day 1 through Cycle 2 Day 22 (each cycle is 28 days))
- Objective Response Rate (ORR)(From Cycle 1 Day 1 until Progressive Disease/Death/or start of new anticancer therapy, up to approximately 3 years)
- Disease control rate (DCR)(From Cycle 1 Day 1 until Progressive Disease/Death/or start of new anticancer therapy, up to approximately 3 years)
- Clinical benefit rate (CBR)(From Cycle 1 Day 1 until Progressive Disease/Death/or start of new anticancer therapy, up to approximately 3 years)
- Best overall response (BoR)(From Cycle 1 Day 1 until Progressive Disease/Death/or start of new anticancer therapy, up to approximately 3 years)
- Duration of Response (DoR)(From Cycle 1 Day 1 until Progressive Disease/Death/or start of new anticancer therapy, up to approximately 3 years)
- Progression-Free Survival (PFS)(From Cycle 1 Day 1 until the first documented objective disease progression or death due to any cause, whichever occurs first, up to approximately 3 years)
- Overall Survival (OS)(From Cycle 1 Day 1 until Death, up to approximately 3 years)
- Duration of stable disease (SD)(From Cycle 1 Day 1 until Progressive Disease/Death/or start of new anticancer therapy, up to approximately 3 years)