Lerapolturev in Recurrent Malignant Glioma

INCLUSION CRITERIA SUMMARY: 1. Patients must have a recurrent (first or second recurrence only, including this recurrence; transformation from a lower grade tumor to a WHO grade IV malignant glioma will be considered a first recurrence) supratentorial WHO grade IV malignant glioma based on imaging studies with measurable disease (a minimum measurement of 1 cm and maximum of 5.5 cm of contrast-enhancing tumor) with prior histopathology consistent with a WHO grade IV malignant glioma confirmed by the site's neuropathologist or the neuropathologist's designate. 2. Male patients who are sexually active are eligible if he and/or his partner(s) meets the criteria outlined in the protocol. Female subjects are eligible if he and/or his partner(s) meets the criteria outlined in the protocol. 3. Age ≥ 18 years of age. 4. Karnofsky Performance Status (KPS) Score ≥ 70%. 5. Prothrombin and Partial Thromboplastin Times ≤ 1.2 x normal prior to biopsy. 6. Total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase ≤ 2.5 x normal prior to biopsy. 7. Neutrophil count ≥ 1000 prior to biopsy. 8. Hemoglobin ≥ 9 prior to biopsy. 9. Platelet count ≥ 100,000/μL unsupported is necessary for eligibility on study; however, because of risks of intracranial hemorrhage with catheter placement, platelet count ≥ 125,000/μL is required for the patient to undergo biopsy and catheter insertion, which can be attained with the help of platelet transfusion. 10. Creatinine ≤ 1.2 x normal range prior to biopsy. 11. Positive serum anti-PV titer prior to biopsy. 12. The patient must have received a boost immunization with trivalent inactivated IPOL™ (Sanofi-Pasteur) at least 1 week, but less than 6 weeks, prior to administration of the study agent. 13. At the time of biopsy, prior to administration of virus, the presence of recurrent tumor must be confirmed by histopathological analysis. 14. A signed IRB-approve informed consent form (ICF). 15. Able to undergo brain MRI with and without contrast. EXCLUSION CRITERIA SUMMARY: 1. Females who are pregnant or breast-feeding. 2. Patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeons, their designate, and the reviewer designated by the sponsor. 3. Patients with severe, active co-morbidity, defined as in the protocol. 4. Patients with a previous history of neurological complications due to PV infection. 5. Patients who have not recovered from the toxic effects of prior chemo- and/or radiation therapy. Guidelines for this recovery period are dependent upon the specific therapeutic agent being used. 6. Patients may not have received tumor treating fields (≤ 1 week), chemotherapy or bevacizumab ≤ 4 weeks \[except for nitrosourea and lomustine (≤ 6 weeks); metronomic dosed chemotherapy, such as daily temozolomide, etoposide or cyclophosphamide (≤ 1 week)\] prior to starting the study drug. 7. Patients may not have received immunotherapy ≤ 4 weeks prior to starting the study drug unless patients have recovered from side effects of such therapy. 8. Patients may not be less than 12 weeks from radiation therapy of the brain, unless progressive disease outside of the radiation field or 2 progressive scans at least 4 weeks apart or histopathologic confirmation. 9. Prior to enrollment, has not completed all standard of care treatments, including surgical procedure and radiation therapy (at least 59Gy) as outlined in the protocol. 10. Patients with neoplastic lesions in the brainstem, cerebellum, or spinal cord; radiological evidence of multiple areas of active (growing) disease (active multifocal disease); tumors with contrast-enhancing tumor component crossing the midline (crossing the corpus callosum); extensive subependymal disease (tumor touching subependymal space is allowed); or extensive leptomeningeal disease (tumor touching leptomeninges is allowed). 11. Patients with undetectable anti-tetanus toxoid immunoglobulin G (IgG). 12. Patients with known history of agammaglobulinemia. 13. Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior to admission for lerapolturev infusion. 14. Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups). 15. Patients with prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin. 16. For patients randomized prior to V7, a known history of hypersensitivity to lomustine, dacarbazine, or any components of lomustine. 17. Patients with active autoimmune disease requiring systemic immunomodulatory treatment within the past 3 months.