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

NCT07076498 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 2025-0876CDMRP-PC250876NCI-2025-04865
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn about the safety and effects of M032 given directly into the tumor in children and adults with DMG and who have received standard-of-care radiation therapy.

Conditions

Glioma

Keywords

Diffuse Midline Glioma; H3 K27-altered; H3 K27M-mutant; Pediatric Brain Tumor; DMG; Diffuse Intrinsic Pontine Glioma; Supratentorial DMG; DIPG; M032; Oncolytic Herpes Simplex Virus; Oncolytic Virus; oHSV; Immunotherapy; Oncolytic Immunotherapy; Viral Immunotherapy; Intratumoral Therapy; Phase 1 Trial; Pediatric Oncology; Neuro-Oncology; Clinical Trial in Children; Translational Research

Outcome Measures

Primary Outcomes (1)

• Safety and Adverse Events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (2)

Adult: For Adult Patients Phase 1 Treatment with Single Injection of M032

EXPERIMENTAL

All patients in both disease cohorts (Cohort 1: Supratentorial DMG; Cohort 2: Pontine DMG) will be enrolled in this single-arm Phase 1 trial and will receive intratumoral administration of M032. Each patient will be treated with a single dose of M032 directly injected into the tumor. There is no placebo or comparator arm. The primary objectives are to evaluate the safety and tolerability of M032 and to determine the recommended Phase 2 dose (RP2D). The two disease cohorts will be assessed independently.

Biological: M032

PED: For Pediatric Patients Phase 1 Treatment with Single Injection of M032

EXPERIMENTAL

All patients in both disease cohorts (Cohort 1: Supratentorial DMG; Cohort 2: Pontine DMG) will be enrolled in this single-arm Phase 1 trial and will receive intratumoral administration of M032. Each patient will be treated with a single dose of M032 directly injected into the tumor. There is no placebo or comparator arm. The primary objectives are to evaluate the safety and tolerability of M032 and to determine the recommended Phase 2 dose (RP2D). The two disease cohorts will be assessed independently.

Biological: M032

Interventions

M032 BIOLOGICAL

M032 is a genetically engineered type 1 herpes simplex virus (HSV-1) that has been demonstrated to be aneurovirulent secondary to deletions of both copies of the γ134.5 gene and modified to express human interleukin-12 (IL-12). Each patient will receive a single intratumoral injection of M032.

Adult: For Adult Patients Phase 1 Treatment with Single Injection of M032; PED: For Pediatric Patients Phase 1 Treatment with Single Injection of M032

Eligibility Criteria

• Age: 36 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 36 months
• Newly diagnosed pathologically proven diffuse midline glioma (DMG) (H3 K27M mutant) or radiographic and/or pathologically proven pontine DMG (tumors with an epicenter in the pontine and diffuse involvement in at least 50% of the axial diameter of the pons)
• Patient must have received standard of care radiation ≥ 4 but ≤ 8 weeks prior to study enrollment Note: The eligibility determination, enrollment, pre-surgical planning, and M032 administration must be completed within 8 weeks of radiation therapy completion.
• The tumor characteristics for enrollment are as follows:
• The lesion must be ≥ 1.0 cm and ≤ 4.0 cm in diameter and surgically accessible as determined by MRI
• For patients diagnosed with supratentorial DMG, tumors larger than 4.0 cm may be eligible if they can be surgically debulked to ≤ 4.0 cm
• Patients must have fully recovered from acute treatment-related toxicities prior to entering this study. The study entry timepoint is defined as the time of consent
• Previous treatment guidelines (if applicable):
• Monoclonal antibody (i.e., bevacizumab): patient must have received last dose ≥ 21 days prior
• Radiation: Patients must have received their last fraction of radiation ≥ 4 weeks and ≤ 8 weeks prior to study entry
• Temozolomide: Patients must have received their last dose of chemotherapy ≥ 4 weeks prior
• Normal hematological, renal, and liver function as defined below:
• Hemoglobin \> 9g/dL
• White blood cell ≥ 3,000/μL
• Absolute neutrophil count ≥ 1000/mm3

You may not qualify if:

• Patients who previously received other investigational agents
• Patients with untreated symptomatic hydrocephalus
• Patients with a radiographic atypical pontine DMG or exophytic glioma, unless biopsy confirmed H3K27M alteration
• Patients with a primary spinal cord tumor
• Acute infection, granulocytopenia, or medical condition precluding surgery
• Pregnant or lactating females: Pregnant women are excluded from this study due to the unknown potential of M032 to cause teratogenic or abortifacient effects. Lactating females are excluded from this study due to the unknown potential risk of adverse effects on both the mother and nursing infants associated with treatment using M032
• Diagnosis of encephalitis or CNS infection \< 12 weeks prior
• Receiving ongoing treatment for encephalitis, CNS infection, or multiple sclerosis
• Tumor involvement which would require ventricular inoculation or would require access through a ventricle to deliver treatment
• Patients may not be on immunosuppressive therapy (for at least 1 week), including corticosteroids at the time of enrollment. Physiological replacement of corticosteroids, intermittent use of bronchodilators, or topical steroids will not be excluded from the study.
• Known HIV seropositivity or known immune deficiency
• Patient with an active herpes infection with clinical symptomology
• Concurrent therapy with any drug active against HSV (acyclovir, valacyclovir, penciclovir, famciclovir, ganciclovir, foscarnet, cidofovir) or any systemic immunosuppressive drug therapy (except physiological replacement of corticosteroids
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen for this trial.
• Concurrent anticancer or investigational drug

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Congressionally Directed Medical Research Programs: collaborator

Study Sites (1)

The University of Texas M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Glioma; Diffuse Intrinsic Pontine Glioma

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Gregory Kane Friedman Friedman, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gregory Friedman, MD

CONTACT

713-835-4467; gkfriedman@mdanderson.org

Kara Kachurak, PNP

CONTACT

713-835-4467; kgkachurak@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2025
• First Posted: July 22, 2025
• Study Start: April 23, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2031
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

US (1)