A Phase 1, Multi-center, Open-label, Dose De-escalation Study to Evaluate the Safety and Efficacy of Talimogene Laherparepvec in Pediatric Subjects With Advanced Non Central Nervous System Tumors That Are Amenable to Direct Injection
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 15
- 试验地点
- 22
- 主要终点
- Percentage of Participants Who Experienced a Dose-limiting Toxicity (DLT)
研究概览
简要总结
This is a phase 1 study to evaluate the safety of intralesional talimogene laherparepvec administration in pediatric subjects with advanced non-CNS tumors that are amenable to direct injection
详细描述
This is a phase 1, multicenter, open-label study of talimogene laherparepvec in pediatric subjects with advanced non-CNS tumors that are amenable to direct injection in the clinical setting. Approximately 18 - 24 pediatric subjects are expected to be enrolled and treated with at least 1 dose of talimogene laherparepvec into 2 cohorts stratified by age. DLT will be evaluated based on at least 9 DLT-evaluable subjects in cohort A1. The DLT evaluation period is 35 days from the initial administration of talimogene laherparepvec.
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
- 2 Years 至 21 Years（Child, 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
Talimogene Laherparepvec (TVEC)
The first dose of talimogene laherparepvec will be administered at a dose of up to 4.0 mL of 10ᶺ6 PFU/mL followed by a dose of up to 4.0 mL of 10ᶺ8 PFU/mL 21 days (+3 days) later. Subsequent doses of up to 4.0 mL of 10ᶺ8 PFU/mL will be administered every 14 days (± 3 days) thereafter. Cohorts will be assigned as follows: Cohort A1 (age 12 to ≤ 21 years). Cohort B1 (age 2 to < 12 years). The DLRT will review the safety data of the first 3 subjects in the older age cohort A1 to decide if the younger age cohort B1 can be opened for enrollment. If dose de-escalation is needed and if permissible based on the incidence of DLTs, additional DLT-evaluable subjects will be enrolled and treated at a lower dose level of talimogene laherparepvec. Dose de-escalation cohorts will be assigned as follows and the same DLT rules will be applied: Cohort A2 (age 12 to ≤ 21 years), Cohort B2 (age 2 to < 12 years).
干预措施: Talimogene Laherparepvec (Drug)
结局指标
主要结局
Percentage of Participants Who Experienced a Dose-limiting Toxicity (DLT)
时间窗: Day 1 to Day 35
All toxicities were graded using the Common Terminology Criteria for Adverse Events version 4.0: * Grade 1: Mild * Grade 2: Moderate * Grade 3: Severe/medically significant but not immediately life-threatening * Grade 4: Life-threatening * Grade 5: Death related to adverse event The occurrence of any of the below was considered a DLT, if judged to be related to talimogene laherparepvec: * Grade 4 non-hematologic toxicity * Grade 3 non-hematologic toxicity that lasted \> 3 days despite optimal supportive care * Any ≥ grade 3 non-hematologic laboratory value if medical intervention was required, the abnormality led to hospitalization or the abnormality persisted for \> 1 week unless deemed not clinically important per both investigator \& sponsor * Febrile neutropenia grade 3/4 * Thrombocytopenia \< 25 x 10\^9/L associated with bleeding event that required intervention * Serious herpetic event * Grade 5 toxicity * Any intolerable toxicity that led to permanent discontinuation of talimogene laherparepvec
次要结局
- Overall Response Rate (ORR)(Every 12 weeks until the end of follow-up; maximum duration of follow-up was 54.51 months)
- Time to Response (TTR)(Every 12 weeks until the end of follow-up; maximum duration of follow-up was 54.51 months)
- Duration of Response (DOR)(Every 12 weeks until the end of follow-up; maximum duration of follow-up was 54.51 months)
- Overall Survival (OS)(Every 12 weeks until the end of follow-up; maximum duration of follow-up was 54.51 months)
- Time to Progression (TTP)(Every 12 weeks until the end of follow-up; maximum duration of follow-up was 54.51 months)
- Progression Free Survival (PFS)(Every 12 weeks until the end of follow-up; maximum duration of follow-up was 54.51 months)