A Phase 1/2a, Open-label, Multicenter, Dose Escalation and Dose Expansion Study Evaluating the Safety, Tolerability, and Efficacy of RZ-001 in Combination With Valganciclovir in Subjects With Glioblastoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 43
- 试验地点
- 6
- 主要终点
- Number of participants with treatment-related adverse events as assessed by NCI-CTCAE
研究概览
简要总结
This is a Phase 1/2a, open-label study to evaluate the safety, tolerability, immunogenicity, and preliminary clinical activity of RZ-001 administered in combination with VGCV in subjects with hTERT-positive GBM.
详细描述
The study consists of 2 parts: a dose-escalation part (Part 1) and a dose-expansion part (Part 2).
Part 1 consists of dose escalation exploring MTD/RP2D for intratumoral (IT) injection.
Part 2 will consist of dose expansion exploring clinical activity for the optimal fixed dose based on the results of Part 1.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Adult males and females
- •Histologically-confirmed grade 4 astrocytoma, GBM, per The 2021 WHO Classification of CNS Tumors.
- •hTERT positive expression confirmed during the screening period
- •ECOG score of ≤ 2
- •Life expectancy ≥ 3 months
排除标准
- •Diagnosis of other malignant tumors within 5 years prior to RZ-001 administration.
- •Have extracranial metastases of the tumor cells
- •Current or history of HIV positive
- •Not suitable for inclusion judged by the investigator
研究组 & 干预措施
Part 1 Cohort 4
RZ-001 Dose 4 and VGCV
干预措施: RZ-001 (Drug)
Part 1 Cohort 1
RZ-001 Dose 1 and VGCV
干预措施: RZ-001 (Drug)
Part 1 Cohort 1
RZ-001 Dose 1 and VGCV
干预措施: VGCV (Combination Product)
Part 1 Cohort 2
RZ-001 Dose 2 and VGCV
干预措施: RZ-001 (Drug)
Part 1 Cohort 2
RZ-001 Dose 2 and VGCV
干预措施: VGCV (Combination Product)
Part 1 Cohort 3
RZ-001 Dose 3 and VGCV
干预措施: RZ-001 (Drug)
Part 1 Cohort 3
RZ-001 Dose 3 and VGCV
干预措施: VGCV (Combination Product)
Part 1 Cohort 4
RZ-001 Dose 4 and VGCV
干预措施: VGCV (Combination Product)
Part 1 Cohort 5
RZ-001 Dose 5 and VGCV
干预措施: RZ-001 (Drug)
Part 1 Cohort 5
RZ-001 Dose 5 and VGCV
干预措施: VGCV (Combination Product)
Part 2
RZ-001 Dose 6 and VGCV
干预措施: RZ-001 (Drug)
Part 2
RZ-001 Dose 6 and VGCV
干预措施: VGCV (Combination Product)
结局指标
主要结局
Number of participants with treatment-related adverse events as assessed by NCI-CTCAE
时间窗: Day 1 to Day 28
Adverse events (AEs) as characterized by type, number, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI-CTCAE\]), timing, seriousness, and relationship to RZ-001
Number of participants with significant laboratory abnormalities as assessed by NCI-CTCAE
时间窗: Day 1 to Day 28
Clinically significant laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI-CTCAE), timing, and relationship to RZ-001
Maximum tolerated dose (MTD) or maximum administered dose (MAD) dose(MAD) and select the recommended Phase 2 dose (RP2D) of RZ-001 in combination with VGCV
时间窗: Day 1 to Day 28
Overall survival (OS)
时间窗: Day 1 to Day 15
Number of dose limiting toxicities (DLTs)
时间窗: Day 1 to Day 28
次要结局
- Change in concentration of serum vascular endothelial growth factor (VEGF)(Day 1 to Day 28)
- Overall response rate (ORR)(Day 1 to Day 15)
- Duration of response (DOR)(Day 1 to Day 15)
- Progression-free survival (PFS) per modified Response Assessment for Neuro-Oncology (mRANO)(Day 1 to Day 15)
- Change in concentration of serum anti-adenovirus antibody(Day 1 to Day 28)
- Overall survival (OS)(Day 1 to Day 15)
- Neurologic function assessment using the Neurologic Assessment in Neuro-Oncology (NANO) scale ranging from 0 to 3 in each assessment domain(Day 1 to Day 15)