Part A: A First-in-Human Single Ascending Dose Study of TRX518 in Subjects With Unresectable Stage III or Stage IV Malignant Melanoma or Other Solid Tumor Malignancies Part B: A Dose-Escalation Study of Multi-dose TRX518 Monotherapy Part C: An Expansion Cohort of Multi-dose TRX518 Monotherapy at the Maximum Tolerated Dose
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Part A: Area under the curve (AUC)
研究概览
简要总结
TRX518-001 is an open label, non-randomized single group assignment, Phase 1 single dose escalation study in adults with biopsy proven unresectable Stage III or Stage IV melanoma or other solid tumor malignancies.
Part A: The study objectives are to determine the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) profiles of TRX518 and to define the maximum tolerated dose at which there are tolerable side effects and/or maximum PK/PD parameter changes.
Subjects will be assigned to a cohort in the order screening is completed. Dose will depend upon the cohort in which a subject is enrolled and cohorts will be dosed consecutively by ascending dose. Part A has been completed.
Part B: A Dose-Escalation Study of Multi-dose TRX518 Monotherapy with objectives including characterization of the safety, tolerability, and pharmacokinetics, as well as, evaluate for evidence of anti-tumor activity and assess TRX518 immunogenicity.
Part C: An Expansion Cohort of Multi-dose TRX518 Monotherapy at the Maximum Tolerated Dose
详细描述
The following visits are required:
Part A:
- Screening visit: 1 to 2 appointments will be conducted to determine eligibility. All or most requirements can be determined from the patient's medical records.
- Baseline visit: within 7 days of the planned study dosing day a baseline physical exam, blood tests and electrocardiogram will be obtained.
- Dosing visit: 1 outpatient visit where TRX518 will be given IV over 1 hour followed by 4 hours of observation and some repeat blood tests.
- Follow up visits: 5 outpatient visits following dosing at 1, 8 and 15 days and 3, 6, 12, and 18 weeks post dosing
- Long term follow-up: 4 brief assessments by medical record review and/or telephone contact at 6, 12, 18, and 24 months post dosing.
- The core study duration is 18 weeks. The follow-up study duration is 24 months.
Parts B & C:
- Screening/Baseline visit: 1 appointment will be conducted to perform testing and evaluations for eligibility within 28 days of the first dosing day.
- Dosing Visits: Each subject will receive IV doses of TRX518 once every other week (e.g., D1 and D15) in 28-day cycles
- Follow up visits: When a patient stops treatment, they will enter the Follow-up Period and have an End of Treatment study visit approximately 30 days after the last dose of study drug. Subsequently, patients will have long-term follow-up approximately every 12 weeks until death or lost to follow up.
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
- 未提供
研究组 & 干预措施
TRX518
干预措施: TRX518 (Biological)
结局指标
主要结局
Part A: Area under the curve (AUC)
时间窗: various timepoints through 1 week post dose
Observations of the distribution, duration of effects and chemical changes of TRX518 in the body and the effects and routes of the body's elimination of TRX518
Part A: Time to peak concentration (Tmax)
时间窗: various timepoints through 1 week post dose
Observations of the distribution, duration of effects and chemical changes of TRX518 in the body and the effects and routes of the body's elimination of TRX518
Part A: Adverse Events
时间窗: through 30 days post last dose
Any adverse change in health or side effect from the initiation of the study drug dose through completion or premature withdrawal
Part A: TRX518 peak concentration (Cmax)
时间窗: various timepoints through 1 week post dose
Observations of the distribution, duration of effects and chemical changes of TRX518 in the body and the effects and routes of the body's elimination of TRX518
Part A: Define a maximum single dose at which there are tolerable side effects and/or maximum PK/PcD parameter changes
时间窗: End of Cycle 1 (Day 28)
Parts B and C: Adverse Events
时间窗: through 30 days post dose
Any adverse change in health or side effect from the initiation of the study drug dose through completion or premature withdrawal
次要结局
- Part A: Evaluate the effect of TRX518 on lymphoid cell subset number and function(At baseline and at various timepoints up to 6 weeks post dose)
- Part A: Evaluate the effect of TRX518 on long-term safety measuring vital signs, tumor status, adverse events(At Months 6, 12, 18 and 24)
- Parts B & C: Assess TRX518 immunogenicity(At baseline and at various timepoints up to end of treatment visit)
- Parts B & C: Time to peak concentration (Tmax)(At each study visit from baseline up to end of treatment visit)
- Parts B & C: Area under the curve (AUC)(At each study visit from baseline up to end of treatment visit)
- Parts B & C: Evaluate the effect of multi-dose TRX518 monotherapy on lymphoid cell subset number and function(At baseline and at various timepoints up to end of treatment visit)
- Parts B & C: TRX518 peak concentration (Cmax)(At each study visit from baseline up to end of treatment visit)
- Part A: Assess TRX518 immunogenicity(At baseline and at various timepoints up to 18 weeks post dose)
- Parts B & C: Evaluate multi-dose TRX18 monotherapy for any evidence of antitumor activity (objective response rate, [ORR] progression free survival [PFS], duration of response and overall survival [OS]; RECIST v1.1 will be utilized(Every 8 weeks while on study treatment and every 12 weeks for survival until death or lost to follow up.)