This is a Phase 1 open label study designed to assess the safety and tolerability of the oncolytic herpes simplex virus 1 (oHSV1) study drug, MVR-C5252, administered intratumorally by convection-enhanced delivery (CED) in patients with recurrent high-grade glioma. Once the safety and maximum tolerated dose (MTD) is established in the dose escalation portion of the trial, a dose expansion cohort at the recommended phase 2 dose (RP2D) in patients with isocitrate dehydrogenase (IDH) wildtype recurrent glioblastoma (GBM) will evaluate preliminary efficacy of the study drug.
Age >18 years of age
Within the enhancing portion or in the vicinity of enhancement of target lesion (i.e., infiltrative disease)
≥ 0.5 cm from ventricles
≥ 1 cm deep into the brain
Prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin
Patients who are pregnant or breastfeeding
Patients with contrast-enhancing tumor crossing the midline, multifocal tumor, infratentorial tumor, tumor in eloquent brain regions, extensive tumor dissemination (subependymal or leptomeningeal), or in unsafe brain regions per the opinion of the treating neurosurgeon
Unstable systemic disease in the opinion of the treating physician.
Sequential
MVR-C5252
Biological/VaccineMVR-C5252 is a genetically modified next generation oncolytic herpes simplex virus 1 (oHSV1) with an active domain of human IL-12 and Fab fragment of anti-PD-1 antibody. This is a Phase 1 open label study designed to determine the safety and tolerability of MVR-C5252. The dose-escalation portion of the study will be conducted in 4 stages to evaluate the safety of infusion and determination of the MTD/RP2D followed by efficacy assessment.
Stage 1: Proportion of patients with dose-limiting toxicity (DLT) during the single infusion
Proportion of patients with dose-limiting toxicity (DLT) during the single infusion
Stage 2: Proportion of patients with dose-limiting toxicity (DLT) during 2 infusions using the internalized Ascenda catheter
Proportion of patients with DLT who have received two infusions on days 1 and 28
Stage 3a: Proportion of patients with dose-limiting toxicity (DLT) after each cycle with two infusions on days 1 and 8
Proportion of patients with DLT who have received two infusions on days 1 and 8
Stage 3b: Determine the MTD/RP2D
Maximal Tolerated Dose/Recommended Phase 2 Dose (MTD/RP2D)
Overall Survival
Day 1 of treatment until death to calculate Median overall survival by the Kaplan-Meier method.
Progression Free Survival
Day 1 of treatment until first documentation of disease progression or death to calculate Median progression free survival by the Kaplan-Meier method.
Click on the lead sponsor to view all of their trials.
