Intratumoral M032 (IL-12-expressing engineered HSV-1) for newly diagnosed diffuse midline glioma after radiation
Phase 1 Trial of Engineered HSV-1 M032 in Children and Adults With Newly Diagnosed Diffuse Midline Glioma After Standard of Care Radiation
This will test whether injecting M032, a modified herpes virus that produces IL-12, directly into the tumor is safe and how it affects children and adults with newly diagnosed diffuse midline glioma after they finish radiation.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 20 (estimated) |
| Ages | 36 Months and up |
| Sex | All |
| Sponsor | M.D. Anderson Cancer Center Academic / other |
| Drugs / interventions | bevacizumab, chemotherapy, radiation, immunotherapy |
| Locations | 1 site (Houston, Texas) |
| Trial ID | NCT07076498 on ClinicalTrials.gov |
What this trial studies
This is a Phase 1, dose-escalation trial giving M032 (an IL-12–expressing engineered HSV-1) directly into accessible tumor lesions by stereotactic intratumoral injection in patients with newly diagnosed diffuse midline glioma after standard radiation. The primary goal is to define safety, tolerability, and the maximum tolerated dose (recommended Phase 2 dose) across supratentorial and pontine cohorts. Secondary measures include radiographic response, progression-free and overall survival, virologic shedding, and systemic immune responses measured by blood tests. Exploratory analyses will examine immune cell populations and checkpoint proteins in available pre- and post-treatment tissue and outcomes by subsequent therapies.
Who should consider this trial
Good fit: Children (age ≥36 months) and adults with newly diagnosed, pathologically or radiographically confirmed diffuse midline glioma (including H3 K27-altered) who completed standard radiation 4–8 weeks earlier and have a surgically accessible lesion between about 1.0–4.0 cm in diameter are ideal candidates.
Not a fit: Patients with tumors that are not surgically accessible, tumors outside the size criteria, unresolved acute treatment toxicities, or those with recurrent disease are less likely to benefit from this protocol.
Why it matters
Potential benefit: If successful, this approach could provoke a local immune response that slows tumor growth and potentially extends survival for patients with diffuse midline glioma.
How similar studies have performed: Early-phase work with oncolytic viruses in adult gliomas has shown acceptable safety and occasional responses, but using an IL-12–expressing HSV-1 in newly diagnosed diffuse midline glioma is largely novel and unproven.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 * Platelets ≥ 100,000/mm3 * PT or PTT ≤ 1.3 x control * Creatinine within normal institutional limits OR creatinine clearance ≥ 60 mL/min/1.73 m2 (cystatin C preferred) for patients with creatinine levels above institutional normal * Total Bilirubin ≤ 1.5 mg/dl * Transaminases \< 3 times above the upper limits of the institutional norm * Patients \< 16 years, Modified Lansky score ≥ 60; patients ≥ 16 years, Karnofsky score ≥ 60 * Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following: * Postmenopausal (no menses in greater than or equal to 12 consecutive months). * History of hysterectomy or bilateral salpingo-oophorectomy. * Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy). * History of bilateral tubal ligation or another surgical sterilization procedure. * Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. * Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of study agent administration. * Written informed consent in accordance with institutional and FDA guidelines must be obtained from the patient or legal guardian Exclusion Criteria: * 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 * Patients with medical contraindications for MRI or MRI contrast agents. * Patients who have received a live vaccine within 30 days prior to planned M032 treatment.
Where this trial is running
Houston, Texas
- The University of Texas M. D. Anderson Cancer Center — Houston, Texas, United States (Recruiting)
Study contacts
- Principal investigator: Gregory Kane Friedman Friedman, MD — M.D. Anderson Cancer Center
- Study coordinator: Gregory Friedman, MD
- Email: gkfriedman@mdanderson.org
- Phone: 713-835-4467
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.