M032 for Brain Tumor

Overseen By Gregory Friedman, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Antivirals, Immunosuppressants

Disqualifiers: Pregnancy, HIV, Hydrocephalus, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 8

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effects of a new treatment called M032, injected directly into brain tumors. It focuses on helping children and adults with diffuse midline glioma (DMG), a type of brain tumor, who have already undergone radiation therapy. The trial will assess the treatment's safety and determine the best dose for future studies. It may suit those with brain tumors at least 1 cm in size, accessible by surgery, and who have recently completed radiation therapy. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial requires that you stop taking any immunosuppressive therapy, including corticosteroids, at least one week before enrollment. If you are on any drugs active against HSV (like acyclovir) or any anticancer or investigational drugs, you will need to stop those as well. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that M032 is likely to be safe for humans?

Research has shown that direct injection of M032 into brain tumors has not caused major side effects. One study found no serious side effects that would prevent doctors from increasing the dose. On average, patients lived about 151 days after treatment, providing insight into their outcomes over time.

As a Phase 1 trial, the primary goal is to determine the treatment's safety and the optimal dose for future studies. Phase 1 trials typically mark the first time a treatment is tested in people, focusing on safety data collection. So far, M032 appears well-tolerated, with most participants not experiencing harmful side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for brain tumors, which often involve surgery, radiation, or chemotherapy, M032 is unique because it involves a direct injection into the tumor itself. This targeted delivery method allows the treatment to act directly where it's needed, potentially reducing side effects associated with more systemic therapies. Researchers are excited about M032 because it aims to determine the optimal dose with a focus on safety and tolerability, which could pave the way for more effective treatments in the future.

What evidence suggests that M032 might be an effective treatment for brain tumors?

Research has shown that M032 is a promising treatment for brain tumors because it targets tumor cells directly. M032 is a specially designed virus that attacks and kills cancer cells without harming normal cells. Early studies indicate that this method can shrink tumors and may help patients live longer. In this trial, all participants will receive a single injection of M032 directly into the tumor. M032 works by multiplying inside the tumor cells, causing them to burst and die. This approach has shown potential in treating similar brain tumors, offering hope for patients with hard-to-treat conditions like DMG. ^{1 6 7 8 9}

Who Is on the Research Team?

Gregory Kane Friedman Friedman, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for children and adults with a specific brain tumor called diffuse midline glioma (DMG), who have finished standard radiation therapy. Participants must be over 3 years old, have good blood, kidney, and liver function, and tumors between 1-4 cm that can be reached surgically. They should not have had certain recent treatments or infections, no HIV or immune deficiencies, not pregnant or breastfeeding, agree to use contraception if of childbearing potential.

Inclusion Criteria

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

My blood, kidney, and liver tests are within normal ranges.

My tumor is between 1.0 and 4.0 cm or can be reduced to this size for surgery.

Exclusion Criteria

Patients who previously received other investigational agents

Known HIV seropositivity or known immune deficiency

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intratumoral injection of M032 during standard of care craniotomy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with follow-up visits and assessments

15 years

Follow-up at 7, 14, and 28 days, then 3, 5, 7, 9, 12, 18, 24, and 36 months, and annually up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• M032

Trial Overview The study tests the safety and effects of M032—an engineered herpes simplex virus type 1—administered directly into the tumor post-standard radiation in patients with DMG. The focus is on understanding how well this treatment works after initial radiotherapy has been completed.

How Is the Trial Designed?

Group I: PED: For Pediatric Patients Phase 1 Treatment with Single Injection of M032 Experimental Treatment 1 Intervention

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.

Group II: Adult: For Adult Patients Phase 1 Treatment with Single Injection of M032 Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Congressionally Directed Medical Research Programs

Collaborator

Trials

59

Recruited

10,600+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07076498

Study Details | NCT07076498 | Engineered HSV-1 M032 ... 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 ...

2. researchgate.net researchgate.net/publication/304069776_Design_of_a_Phase_I_Clinical_Trial_to_Evaluate_M032_a_Genetically_Engineered_HSV-1_Expressing_IL-12_in_Patients_with_RecurrentProgressive_Glioblastoma_Multiforme_Anaplastic_Astrocytoma_or_Gliosarcoma

Design of a Phase I Clinical Trial to Evaluate M032 ... M032 is a second-generation oncolytic herpes simplex virus (oHSV) that selectively replicates in tumor cells. M032 kills tumor cells directly through ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9519005/

Immunotherapy approaches for the treatment of diffuse ... Median overall survival is less than 12 months with a 90% mortality rate at 2 years from diagnosis. Research into the underlying tumor biology and numerous ...

4. moonlab.engin.umich.edu moonlab.engin.umich.edu/wp-content/uploads/sites/584/2022/09/78-Garcia-Fabiani-ExpOpInvestDrugs-2020.pdf

Immunotherapy for gliomas - Moon Lab Unfortunately, clinical trials have not yet yielded consistent results for glioma patients. This could be attributed to our limited understanding of the complex ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1937644823000588

Oncolytic viruses as treatment for adult and pediatric high- ... In this review, we summarize completed and ongoing clinical trials of oncolytic virotherapy for adult and pediatric malignant gliomas in terms of safety and ...

6. withpower.com withpower.com/trial/phase-1-glioma-11-2025-be486

M032 for Brain Tumor · Info for Participants 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 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8383155/

Safety and interim survival data after intracranial ... The median overall survival from the date of treatment was 151 days (± 78 days). No significant adverse events attributable to M032 or dose-limiting toxicities ...

8. mayoclinic.org mayoclinic.org/diseases-conditions/diffuse-midline-glioma/symptoms-causes/syc-20584386

Diffuse midline glioma - Symptoms and causes Diffuse midline glioma (DMG) is a rare type of cancerous brain tumor. It's most common in children between the ages of 5 and 10 years old ...

9. tandfonline.com tandfonline.com/doi/full/10.1080/2162402X.2022.2124058

Immunotherapy approaches for the treatment of diffuse ... Diffuse midline gliomas (DMG) are a highly aggressive and universally fatal subgroup of pediatric tumors responsible for the majority of childhood brain tumor ...