A Phase I, Open Label, Multicenter Study of the Safety and Efficacy of MIW815 (ADU-S100) Administered by Intratumoral Injection to Patients With Advanced/Metastatic Solid Tumors or Lymphomas
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 47
- 试验地点
- 7
- 主要终点
- Recommended dose
研究概览
简要总结
The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics and antitumor activity of MIW815 (ADU-S100) administered via intratumoral injection as a single agent and in combination with ipilimumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Willing to undergo tumor biopsies from injected and distal lesions
- •Must have two biopsy accessible lesions:
- •* one lesion must be ≥10 mm and <100 mm in longest diameter, accessible for repeated intratumoral (IT) injection and accessible for baseline and on-treatment biopsies.
- •a second (distal) lesion must be accessible for baseline and on-treatment biopsy and must be distinct from the injected lesion.
- •tumors encasing major vascular structures (i.e., carotid artery or tumors close to other vital organs), are not considered appropriate
排除标准
- •Patients who require local palliative measures such as XRT or surgery
- •Symptomatic or untreated leptomeningeal disease.
- •Presence of symptomatic central nervous system (CNS) metastases
- •Impaired cardiac function or clinically significant cardiac disease
- •Active autoimmune disease or a documented history of autoimmune disease, except vitiligo or resolved childhood asthma/atopy.
- •Active infection requiring systemic antibiotic therapy.
- •Known history of Human Immunodeficiency Virus (HIV) infection.
- •Active Epstein-Barr virus (EBV), hepatitis B virus (HBV) or hepatitis C virus (HCV)
- •Malignant disease, other than that being treated in this study.
研究组 & 干预措施
Dose escalation monotherapy
ADU-S100 administered intratumorally on Days 1, 8 and 15 of each 28-day cycle until unacceptable toxicity, progressive disease and/or treatment is discontinued; starting dose 50 micrograms
干预措施: ADU-S100 (Drug)
Dose escalation combination
ADU-S100 administered intratumorally on Days 1 and 8 of each 21-day cycle (starting dose 200 micrograms) and ipilimumab, i.v., (3 mg/kg) on day 1 of each 21-day cycle for the first 4 cycles. Dosing is continued until unacceptable toxicity, progressive disease and/or treatment is discontinued
干预措施: ADU-S100 (Drug)
Dose escalation combination
ADU-S100 administered intratumorally on Days 1 and 8 of each 21-day cycle (starting dose 200 micrograms) and ipilimumab, i.v., (3 mg/kg) on day 1 of each 21-day cycle for the first 4 cycles. Dosing is continued until unacceptable toxicity, progressive disease and/or treatment is discontinued
干预措施: ipilimumab (Biological)
结局指标
主要结局
Recommended dose
时间窗: 6 months from study start
Using maximum tolerated dose to identify the recommended dose for future studies
Safety: Number of patients reporting treatment-related adverse events that qualify as dose-limiting toxicities
时间窗: 6 months from study start
Number of patients reporting treatment-related adverse events that qualify as dose-limiting toxicities
次要结局
- Pharmacokinetics measured through plasma concentrations(6 months from study start)
- measurement of CD8-TIL counts(6 months from study start)
- RNA expression analysis of IFN gamma and immunomodulatory genes(6 months from study start)