A Study to Evaluate the Safety, Tolerability and Efficacy of RZ-001 With Valganciclovir (VGCV) in Subjects With Glioblastoma

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат RZ-001
  Recombinant adenovirus harboring the modified ribozyme construct with HSV-tk as a therapeutic transgene
• Комбинированный продукт VGCV
  VGCV, used in a subject after RZ-001 administration, is a nucleoside analog that is metabolized by HSV-tk and other cellular kinases to form the cytotoxic nucleotide analog ganciclovir triphosphate. An approved oral VGCV will be used in the proposed clinical study of RZ-001.

Первичные конечные точки

• Number of dose limiting toxicities (DLTs) [Срок оценки: Day 1 to Day 28]
• 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 [Срок оценки: Day 1 to Day 28]
• Number of participants with treatment-related adverse events as assessed by NCI-CTCAE [Срок оценки: Day 1 to Day 28]
• Number of participants with significant laboratory abnormalities as assessed by NCI-CTCAE [Срок оценки: Day 1 to Day 28]
• Overall survival (OS) [Срок оценки: Day 1 to Day 15]

Вторичные конечные точки (7)

• Change in concentration of serum vascular endothelial growth factor (VEGF) [Срок оценки: Day 1 to Day 28]
• Change in concentration of serum anti-adenovirus antibody [Срок оценки: Day 1 to Day 28]
• Overall response rate (ORR) [Срок оценки: Day 1 to Day 15]
• Duration of response (DOR) [Срок оценки: Day 1 to Day 15]
• Progression-free survival (PFS) per modified Response Assessment for Neuro-Oncology (mRANO) [Срок оценки: Day 1 to Day 15]
• Overall survival (OS) [Срок оценки: 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 [Срок оценки: Day 1 to Day 15]

Критерии участия

Критерии включения

• 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
• KPS ≥ 60
• Life expectancy ≥ 3 months

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

South Korea · 6 центров

• The Catholic University of Korea, Incheon St. Mary's Hospital — Incheon
• Gachon University Gil Medical Center — Incheon
• Seoul National University Bundang Hospital — Seongnam-si
• Severance Hospital, Yonsei University Health System — Seoul
• Asan Medical Center — Seoul
• Samsung Medical Center — Seoul

Идентификаторы

NCT: NCT06102525 · RZ-001-201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗