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

Sponsor
Rznomics, Inc. (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT06102525
Collaborator
(none)
43
Enrollment
6
Arms
67
Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
43 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Anticipated Study Start Date :
Oct 1, 2023
Anticipated Primary Completion Date :
Mar 1, 2029
Anticipated Study Completion Date :
May 1, 2029

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of dose limiting toxicities (DLTs) [Day 1 to Day 28]

    2. 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]

    3. 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

    4. 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

    5. Overall survival (OS) [Day 1 to Day 15]

    Secondary Outcome Measures

    1. Change in concentration of serum vascular endothelial growth factor (VEGF) [Day 1 to Day 28]

    2. Change in concentration of serum anti-adenovirus antibody [Day 1 to Day 28]

    3. Overall response rate (ORR) [Day 1 to Day 15]

    4. Duration of response (DOR) [Day 1 to Day 15]

    5. Progression-free survival (PFS) per modified Response Assessment for Neuro-Oncology (mRANO) [Day 1 to Day 15]

    6. Overall survival (OS) [Day 1 to Day 15]

    7. 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

    1. Concentration of adenovirus DNA in Plasma at specified timepoints [Day 1 to Day 28]

    2. Change in concentration of serum anti-adenovirus antibody [Day 1 to Day 28]

    3. 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)

    4. 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)

    5. Concentration of biomarker in fresh tumor biopsy tissue [Day 1 to Day 28]

      Tumor-related RNA and T cell infiltration and activation

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Rznomics, Inc.

    Investigators

    • Principal Investigator: Doo Sik Kong, Samsung Medical Center
    • Principal Investigator: Chang Ki Hong, Asan Medical Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Rznomics, Inc.
    ClinicalTrials.gov Identifier:
    NCT06102525
    Other Study ID Numbers:
    • RZ-001-201
    First Posted:
    Oct 26, 2023
    Last Update Posted:
    Oct 26, 2023
    Last Verified:
    Oct 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Additional relevant MeSH terms:
    Glioblastoma
    Valganciclovir

    Study Results

    No Results Posted as of Oct 26, 2023