The PuMP Trial: "A Multistage Phase 1 Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of the Oncolytic HSV1 MVR-C5252 in Patients With Recurrent High-Grade Glioma"
Duke University
Summary
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.
Description
Oncolytic HSV1 (oHSV1) was the first viral vector studied in clinical trials to treat malignant glioma with positive outcomes for tolerability and potential clinical benefits. MVR-C5252 is a genetically modified next generation oHSV1 with an active domain of human IL-12 and Fab fragment of anti-PD-1 antibody. During viral replication, IL-12 and anti-PD-1 antibody are expressed and secreted into the tumor microenvironment, acting synergistically by increasing the T cell infiltration, converting the cold (immune suppressing) tumor to hot (immune active) tumor, and inducing anti-tumor specific im…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Age \>18 years of age 2. Disease recurrence of at least 1x1cm and a maximum of 3x3cm of enhancing tumor: Dose escalation portion: patients with recurrent high-grade glioma, IDH wt or IDH mutated, grade 3 or grade 4 based on imaging. Dose expansion portion: Recurrent, IDH wt, glioblastoma, WHO grade 4. Diagnosis has be made using the 2021 WHO Classification of Tumors of the CNS. 3. The neurosurgeon must confirm (a) the tumor location (\> 1 cm from eloquent brain), (b) that the placement of infusion catheter within or through the progressive enhancing tumor is fea…
Interventions
- BiologicalMVR-C5252
MVR-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.
Locations (2)
- Memorial Sloan KetteringNew York, New York
- Duke UniversityDurham, North Carolina