Clinical trial NCT06102525: A Study to Evaluate the Safety, Tolerability and Efficacy of RZ-001 with Valganciclovir (VGCV) in Subjects with Glioblastoma
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Glioblastoma
Lead sponsor: Rznomics, Inc.
Sponsor class: OTHER
First posted: 2023-10-26
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of dose limiting toxicities (DLTs)
timeFrame: Day 1 to Day 28
measure: 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
timeFrame: Day 1 to Day 28
measure: Number of participants with treatment-related adverse events as assessed by NCI-CTCAE
timeFrame: Day 1 to Day 28
measure: Number of participants with significant laboratory abnormalities as assessed by NCI-CTCAE
timeFrame: Day 1 to Day 28
measure: Overall survival (OS)
timeFrame: Day 1 to Day 15
Secondary outcomes:
measure: Change in concentration of serum vascular endothelial growth factor (VEGF)
timeFrame: Day 1 to Day 28
measure: Change in concentration of serum anti-adenovirus antibody
timeFrame: Day 1 to Day 28
measure: Overall response rate (ORR)
timeFrame: Day 1 to Day 15
measure: Duration of response (DOR)
timeFrame: Day 1 to Day 15
measure: Progression-free survival (PFS) per modified Response Assessment for Neuro-Oncology (mRANO)
timeFrame: Day 1 to Day 15
measure: Overall survival (OS)
timeFrame: Day 1 to Day 15
measure: Neurologic function assessment using the Neurologic Assessment in Neuro-Oncology (NANO) scale ranging from 0 to 3 in each assessment domain
timeFrame: Day 1 to Day 15
Other outcomes:
measure: Concentration of adenovirus DNA in Plasma at specified timepoints
timeFrame: Day 1 to Day 28
measure: Change in concentration of serum anti-adenovirus antibody
timeFrame: Day 1 to Day 28
measure: Change in concentration of serum cytokines
timeFrame: Day 1 to Day 28
measure: Concentration of biomarker in peripheral blood
timeFrame: Day 1 to Day 28
measure: Concentration of biomarker in fresh tumor biopsy tissue
timeFrame: Day 1 to Day 28
Locations:
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
References: