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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: RZ-001; Combination product: VGCV

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.

• Study Type: Interventional
• Enrollment (Estimated): 43
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Rznomics Inc.; Phone Number: +82317068730; Email: rznomics@rznomics.com
• Study Contact Backup: Name: Hyunjin Yoon; Phone Number: +82-31-701-8735; Email: hjyoon@rznomics.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Cohort 1; RZ-001 Dose 1 and VGCV	Drug: RZ-001; Recombinant adenovirus harboring the modified ribozyme construct with HSV-tk as a therapeutic transgene; Other Names: Ad-ECRT-122T; 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.; Other Names: Valganciclovir
Experimental: Part 1 Cohort 2; RZ-001 Dose 2 and VGCV	Drug: RZ-001; Recombinant adenovirus harboring the modified ribozyme construct with HSV-tk as a therapeutic transgene; Other Names: Ad-ECRT-122T; 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.; Other Names: Valganciclovir
Experimental: Part 1 Cohort 3; RZ-001 Dose 3 and VGCV	Drug: RZ-001; Recombinant adenovirus harboring the modified ribozyme construct with HSV-tk as a therapeutic transgene; Other Names: Ad-ECRT-122T; 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.; Other Names: Valganciclovir
Experimental: Part 1 Cohort 4; RZ-001 Dose 4 and VGCV	Drug: RZ-001; Recombinant adenovirus harboring the modified ribozyme construct with HSV-tk as a therapeutic transgene; Other Names: Ad-ECRT-122T; 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.; Other Names: Valganciclovir
Experimental: Part 1 Cohort 5; RZ-001 Dose 5 and VGCV	Drug: RZ-001; Recombinant adenovirus harboring the modified ribozyme construct with HSV-tk as a therapeutic transgene; Other Names: Ad-ECRT-122T; 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.; Other Names: Valganciclovir
Experimental: Part 2; RZ-001 Dose 6 and VGCV	Drug: RZ-001; Recombinant adenovirus harboring the modified ribozyme construct with HSV-tk as a therapeutic transgene; Other Names: Ad-ECRT-122T; 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.; Other Names: Valganciclovir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Overall survival (OS)		Day 1 to Day 15

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in concentration of serum anti-adenovirus antibody		Day 1 to Day 28
Concentration of adenovirus DNA in Plasma at specified timepoints		Day 1 to Day 28
Change in concentration of serum cytokines	Serum cytokines including interleukins 1 (IL-1), IL-6, IL-10, IL-27, interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α)	Day 1 to Day 28
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
Concentration of biomarker in fresh tumor biopsy tissue	Tumor-related RNA and T cell infiltration and activation	Day 1 to Day 28

Collaborators and Investigators

• Sponsor: Rznomics, Inc.
• Investigators: Principal Investigator: Doo Sik Kong, Samsung Medical Center; Principal Investigator: Chang Ki Hong, Asan Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: June 23, 2023
• First Submitted That Met QC Criteria: October 22, 2023
• First Posted (Actual): October 26, 2023

Study Record Updates

• Last Update Posted (Actual): October 26, 2023
• Last Update Submitted That Met QC Criteria: October 22, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Anti-Infective Agents; Antiviral Agents; Valganciclovir
• Other Study ID Numbers: RZ-001-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes