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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1 Cohort 1 | Experimental | RZ-001 Dose 1 and VGCV |
|
| Part 1 Cohort 2 | Experimental | RZ-001 Dose 2 and VGCV |
|
| Part 1 Cohort 3 | Experimental | RZ-001 Dose 3 and VGCV |
|
| Part 1 Cohort 4 | Experimental | RZ-001 Dose 4 and VGCV |
|
| Part 1 Cohort 5 | Experimental | RZ-001 Dose 5 and VGCV |
|
| Part 2 | Experimental | RZ-001 Dose 6 and VGCV |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RZ-001 | Drug | Recombinant adenovirus harboring the modified ribozyme construct with HSV-tk as a therapeutic transgene |
|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | |
| Measure | Description | Time Frame |
|---|---|---|
| Concentration of adenovirus DNA in Plasma at specified timepoints | Day 1 to Day 28 | |
| Change in concentration of serum anti-adenovirus antibody | Day 1 to Day 28 | |
| Change in concentration of serum cytokines |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Rznomics Inc. | Contact | +82317068730 | rznomics@rznomics.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Catholic University of Korea, Incheon St. Mary's Hospital | Recruiting | Incheon | 21431 | South Korea |
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|
| VGCV | Combination Product | 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. |
|
|
| 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 |
| 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 |
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 |
| Gachon University Gil Medical Center | Recruiting | Incheon | 21565 | South Korea |
|
| Seoul National University Bundang Hospital | Recruiting | Seongnam-si | 13620 | South Korea |
|
| Severance Hospital, Yonsei University Health System | Recruiting | Seoul | 03722 | South Korea |
|
| Asan Medical Center | Recruiting | Seoul | 05505 | South Korea |
|
| Samsung Medical Center | Recruiting | Seoul | 06351 | South Korea |
|
| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
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| ID | Term |
|---|---|
| D000077562 | Valganciclovir |
| ID | Term |
|---|---|
| D015774 | Ganciclovir |
| D000212 | Acyclovir |
| D006147 | Guanine |
| D007042 | Hypoxanthines |
| D011688 | Purinones |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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