Glioblastoma
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGRZ-001
Recombinant adenovirus harboring the modified ribozyme construct with HSV-tk as a therapeutic transgene
COMBINATION_PRODUCTVGCV
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.
Sponsors
Rznomics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment-related adverse events as assessed by NCI-CTCAE | 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 dose limiting toxicities (DLTs) | 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 | Day 1 to Day 28 | — |
| Overall survival (OS) | Day 1 to Day 15 | — |
| Number of participants with significant laboratory abnormalities as assessed by NCI-CTCAE | 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 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Duration of response (DOR) | Day 1 to Day 15 |
| Change in concentration of serum vascular endothelial growth factor (VEGF) | Day 1 to Day 28 |
| Change in concentration of serum anti-adenovirus antibody | Day 1 to Day 28 |
| Overall response rate (ORR) | Day 1 to Day 15 |
| Progression-free survival (PFS) per modified Response Assessment for Neuro-Oncology (mRANO) | Day 1 to Day 15 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Concentration of adenovirus DNA in Plasma at specified timepoints | Day 1 to Day 28 | — |
| Concentration of biomarker in fresh tumor biopsy tissue | Day 1 to Day 28 | Tumor-related RNA and T cell infiltration and activation |
| Concentration of biomarker in peripheral blood | Day 1 to Day 28 | Activation of immune cell subsets (including but not limited to cluster of differentiation 3 \[CD3\], CD4, CD8, B cell, natural killer \[NK\] cell) |
| Change in concentration of serum cytokines | Day 1 to Day 28 | Serum cytokines including interleukins 1 (IL-1), IL-6, IL-10, IL-27, interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α) |
| Change in concentration of serum anti-adenovirus antibody | Day 1 to Day 28 | — |
Countries
South Korea
Contacts
Primary ContactRznomics Inc.
Outcome results
None listed