An Open-label, Multi-center, Dose-escalation and Expansion Study to Evaluate the Safety and Efficacy of ONO-7579 in Patients With Advanced Solid Tumors/ NTRK Gene Fusion Positive Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 5
- 主要终点
- Part A: Clinically significant changes in vital signs and electrocardiogram - including the evaluation of the QT interval
研究概览
简要总结
This study will determine the safety and maximum tolerated dose of ONO-7579 in patients with advanced solid tumors, and evaluate efficacy of ONO-7579 in patients with advanced solid tumors harboring NTRK gene fusions.
详细描述
The trial was designed to be a Phase 1/2 trial, but was terminated without progressing to Phase 2.
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
- •Radiotherapy within two weeks prior to study entry
- •Major surgery (excluding placement of vascular access) within 4 weeks before the first dose of study treatment
- •Spinal cord compression or brain metastases unless treated and radiologically stable for >6 weeks post treatment and not requiring steroids for at least 4 weeks prior to start of study treatment
- •As judged by the Investigator, any evidence of severe or uncontrolled psychiatric disease or systemic diseases, including history of suicide attempt or current suicidal ideation or behavior, active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
- •Concurrent treatment with another investigational agent or participated in another investigational trial within 30 days of study entry
- •Diagnosed or treated for a malignancy other than the tumor under investigation in the study within 5 years, or who were previously diagnosed with a malignancy other than that required for the study and have any radiographic or biochemical marker evidence of that malignancy. Patients with completely resected basal cell carcinoma, squamous cell carcinoma of the skin, or in situ malignancy are not excluded.
- •Clinically significant cardiovascular disease, including:
- •History of myocardial infarction, acute coronary syndromes (including unstable angina), or coronary angioplasty/stenting/bypass grafting within the past 6 months.
- •History of Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system
- •Severe cardiac arrhythmia requiring medication or other severe conduction abnormalities (e.g. clinically significant QT prolongation or Torsade de pointes)
- •Uncontrolled hypertension
- •Clinically significant valvular disease, cardiomegaly, ventricular hypertrophy, or cardiomyopathy
- •QT prolongation defined as a QTcF interval >470 msec or other significant ECG abnormalities including 2nd degree (type II) or 3rd degree AV block or bradycardia (ventricular rate <50 beats/min) on 12-lead ECG at screening
- •Serious concurrent medical conditions, including serious active infection, in the opinion of the investigator
- •Female patients who are pregnant or breast feeding
研究组 & 干预措施
ONO-7579 Part A
Single Ascending doses of ONO-7579
干预措施: ONO-7579 (Drug)
ONO-7579 Part B
Expansion phase of ONO-7579
干预措施: ONO-7579 (Drug)
结局指标
主要结局
Part A: Clinically significant changes in vital signs and electrocardiogram - including the evaluation of the QT interval
时间窗: up to 28 days
To investigate the safety and tolerability of ONO-7579 to determine MTD/RCD
Part A: Clinically significant changes in neurological examinations
时间窗: up to 28 days
To investigate the safety and tolerability of ONO-7579 to determine MTD/RCD
Part A: Incidence, nature and severity of Adverse Events
时间窗: up to 28 days
To investigate the safety and tolerability of ONO-7579 to determine MTD/RCD
Part A: Clinically significant changes in physical examinations
时间窗: up to 28 days
To investigate the safety and tolerability of ONO-7579 to determine MTD/RCD
Part B: Overall Response Rate (ORR)
时间窗: up to 24 months
Assessed by Independent Central Review using RECIST 1.1 or RANO criteria
次要结局
- Part A and B Pharmacokinetics (Tmax)(Day 1, 2, 7, 14 and 28)
- Part A and B Pharmacokinetics (AUC)(Day 1, 2, 7, 14 and 28)
- Part A Duration of Response (DoR)(up to 28 days)
- Part A and B Pharmacokinetics (Cmax)(Day 1, 2, 7, 14 and 28)
- Part A and B Pharmacokinetics (Ctrough)(Day 1, 2, 7, 14 and 28)
- Part B Overall Survival (OS)(up to 24 months)
- Part B Time to Progression (TTP)(up to 24 months)
- Part B Incidence, nature and severity of Adverse Events(up to 24 months)
- Part B: Clinically significant changes in neurological examinations(up to 24 months)
- Part A and B Pharmacokinetics (T1/2)(Day 1, 2, 7, 14 and 28)
- Part A Overall Response Rate (ORR)(up to 28 days)
- Part A Progression Free Survival (PFS)(up to 28 days)
- Part B Time to Response (TTR)(up to 24 months)
- Part B: Clinically significant changes in physical examinations(up to 24 months)
- Part B Progression Free Survival (PFS)(up to 24 months)
- Part B: Clinically significant changes in vital signs and electrocardiogram - including the evaluation of the QT interval(up to 24 months)