A Phase Ib, Open Label, Multicenter Study of the Safety and Efficacy of MIW815 (ADU-S100) Administered by Intratumoral Injection With PDR001 to Patients With Advanced/Metastatic Solid Tumors or Lymphomas
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 106
- 试验地点
- 4
- 主要终点
- Incidence of dose limiting toxicities (DLTs)
研究概览
简要总结
The purpose of this study was to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics and antitumor activity of MIW815 (ADU-S100) in combination with PDR001.
详细描述
This was a Phase Ib, multi-center, open-label study to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of MIW815(ADU-S100) in combination with the PD-1 checkpoint inhibitor PDR001. Two different schedules were explored in two dose escalation groups in accessible cutaneous or subcutaneous lesions. The optional dose confirmation group exploring intratumoral injection of viscerally located lesions was not opened due to the program's early termination.
Group A included patients with accessible solid tumors and lymphomas. This group received a fixed dose of PDR001 i.v. on day 1 of every 28 day cycle and intratumoral injections of MIW815 (ADU-S100) on days 1, 8 and 15 of every 28 day cycle. Group B included patients with accessible solid tumors and lymphomas. This group received a fixed dose of PDR001 i.v. on day 1 of every 28 day cycle and an intratumoral injection of MIW815 (ADU-S100) on day 1 of every 28 day cycle.
Once the dose and dose schedule had been confirmed, the plan was to open the dose expansion part of the study. However, the expansion phase of the study was not opened to enrollment due to the program's early termination.
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
- •ECOG ≤ 1 Willing to undergo tumor biopsies from injected and distal lesions
- •Must have two biopsy accessible lesions:
排除标准
- •Symptomatic or untreated leptomeningeal disease. Presence of symptomatic central nervous system 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 infection. Active Epstein-Barr virus, hepatitis B virus or hepatitis C virus Malignant disease, other than that being treated in this study
研究组 & 干预措施
Dosing Schedule A
Patients were treated with MIW815 (ADU-S100) via intratumoral injection for 3 weeks followed by one week off in combination with a fixed intravenous dose of PDR001 given once per month
干预措施: MIW815 (Drug)
Dosing Schedule A
Patients were treated with MIW815 (ADU-S100) via intratumoral injection for 3 weeks followed by one week off in combination with a fixed intravenous dose of PDR001 given once per month
干预措施: PDR001 (Biological)
Dosing Schedule B
Patients were treated with MIW815 (ADU-S100) via intratumoral injection given once a month in combination with a fixed intravenous dose of PDR001 given once per month
干预措施: MIW815 (Drug)
Dosing Schedule B
Patients were treated with MIW815 (ADU-S100) via intratumoral injection given once a month in combination with a fixed intravenous dose of PDR001 given once per month
干预措施: PDR001 (Biological)
结局指标
主要结局
Incidence of dose limiting toxicities (DLTs)
时间窗: 24 months
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment with the combination of MIW815 (ADU-S100) and PDR001
次要结局
- Duration of Response (DOR)(36 months)
- AUC inf(36 months)
- AUC tau(36 months)
- Overall response rate (ORR)(36 months)
- Tumor infiltrating lymphocytes (TIL)(36 months)
- T1/2(36 months)
- Progression free survival (PFS)(36 months)
- AUC last(36 months)
- Tmax(36 months)
- Lambda_z(36 months)
- CL/F(36 months)
- Vz/F(36 months)
- Best overall response (BOR)(36 months)
- Disease control rate (DCR)(36 months)
- Time to response (TTR)(36 months)
- Cmax(36 months)