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

Glioblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06102525
• Other study ID #: RZ-001-201
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: October 2023
• Est. completion date: May 2029

Study information

• Verified date: October 2023
• Source: Rznomics, Inc.
• Contact: Rznomics Inc.
• Phone: +82317068730
• Email: rznomics[@]rznomics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 43
• Est. completion date: May 2029
• Est. primary completion date: March 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Glioblastoma

Intervention

Drug:
• RZ-001
Recombinant adenovirus harboring the modified ribozyme construct with HSV-tk as a therapeutic transgene

Combination Product:
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Rznomics, Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Concentration of adenovirus DNA in Plasma at specified timepoints		Day 1 to Day 28
Other	Change in concentration of serum anti-adenovirus antibody		Day 1 to Day 28
Other	Change in concentration of serum cytokines	Serum cytokines including interleukins 1 (IL-1), IL-6, IL-10, IL-27, interferon gamma (IFN-?), tumor necrosis factor alpha (TNF-a)	Day 1 to Day 28
Other	Concentration of biomarker in peripheral blood	Activation of immune cell subsets (including but not limited to cluster of differentiation 3 [CD3], CD4, CD8, B cell, natural killer [NK] cell)	Day 1 to Day 28
Other	Concentration of biomarker in fresh tumor biopsy tissue	Tumor-related RNA and T cell infiltration and activation	Day 1 to Day 28
Primary	Number of dose limiting toxicities (DLTs)		Day 1 to Day 28
Primary	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
Primary	Number of participants with treatment-related adverse events as assessed by NCI-CTCAE	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	Day 1 to Day 28
Primary	Number of participants with significant laboratory abnormalities as assessed by NCI-CTCAE	Clinically significant laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI-CTCAE), timing, and relationship to RZ-001	Day 1 to Day 28
Primary	Overall survival (OS)		Day 1 to Day 15
Secondary	Change in concentration of serum vascular endothelial growth factor (VEGF)		Day 1 to Day 28
Secondary	Change in concentration of serum anti-adenovirus antibody		Day 1 to Day 28
Secondary	Overall response rate (ORR)		Day 1 to Day 15
Secondary	Duration of response (DOR)		Day 1 to Day 15
Secondary	Progression-free survival (PFS) per modified Response Assessment for Neuro-Oncology (mRANO)		Day 1 to Day 15
Secondary	Overall survival (OS)		Day 1 to Day 15
Secondary	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