Engineered HSV-1 M032 for the Treatment of Children and Adults With Newly Diagnosed Diffuse Midline Glioma After Standard of Care Radiation

Description

Primary Objective:

I. To assess the safety and tolerability of IL-12-expressing HSV-1 NSC 733972 (M032) administered intratumorally via stereotactic intratumoral injection in children and adults with a diagnosis of diffuse midline glioma (DMG) after receiving standard of care radiation.To determine the maximum tolerated dose (MTD), which will serve as the recommended Phase 2 dose (RP2D). This will include two cohorts: supratentorial DMG H3K27-altered and pontine DMG.

Secondary Objective:

I. Obtain preliminary information concerning the potential efficacy of M032 by assessing longitudinal changes in radiographic response, progression free and overall survival, and performance scale.

II. To survey for virologic shedding in saliva, conjunctiva, and blood. III. To evaluate immunologic responses to M032 by assessing HSV antibody titers and changes from baseline in circulating peripheral blood immune cells, cytokines, and chemokines by longitudinal sampling.

Exploratory Objectives:

I. To evaluate pre- and post-treatment tissue for immune cell populations and checkpoint proteins in patients who are amendable to and meet criteria for resection/biopsy while on study.

II. To assess overall survival (OS) in subgroups of patients based on therapies received after M032 (surgery versus no surgery; reirradiation versus no reirradiation, immunotherapy versus [vs] no immunotherapy).

OUTLINE: This is a dose escalation study of M032.

Patients receive M032 intratumorally (IT) on day 0 over 5 minutes at the time of standard of care (SOC) craniotomy. Patients undergo magnetic resonance imaging (MRI), as well as saliva, conjunctival secretions, blood collection throughout the trial. Patients may undergo tissue biopsy on study.

After completion of study treatment, patients are followed up at 7, 14, and 28 days, then 3, 5, 7, 9, 12, 18, 24 and 36 months, and then annually up to 15 years.