Intratumoral DNX-2401 for High Grade Pediatric Brain Tumors

Inclusion Criteria:

* The participant or participant's parents or legally acceptable representatives (if applicable) provides written informed consent for the trial and the pediatric participant provides writ-ten assent, where applicable, based on age and country requirements.
* Patients with recurrent or refractory high grade malignant brain tumors (high grade glioma, embryonal CNS tumors \[medulloblastomas, ATRT, EMTR, pineoblastoma\], and ependymomas) diagnosis based on initial histopathological diagnosis and further clinical and radiological fol-low-up, in whom gross total resection is not feasible, and with a life expectancy of at least 16 weeks at the time of consent.
* Recurrences within the radiation field will be considered if there is confirmed growth of the lesion in two consecutive MRI or if they occur at least 12 weeks after completion of ra-diation therapy, or if there is clear histopathological confirmation of tumor recurrence.
* Male and female participants age ≥ 1 years and ≤ 25 years.
* A single measurable lesion longer than 10 mm in two perpendicular diameters, considered by the investigator to be accessible for safe stereotactic biopsy and virus injection.
* Lansky Performance Status (LPS) ≥ 60 for participants \< 16 years, or Karnofsky Performance Status (KPS) ≥ 60 for participants ≥ 16 years.
* No other chemotherapy or immunotherapy in the 4 weeks before inclusion.
* Steroids: free off or requiring decreasing or stable corticosteroid dose (≥ 0.05 mg/kg dexa-methasone daily, or equivalent for other steroids) in the 2 weeks before DNX-2401 admin-istration.
* Radiation: no craniospinal irradiation, total body irradiation nor focal irradiation in the 6 weeks before inclusion.
* Autologous Stem Cell Transplantation: patients must be ≥ 3 months post-transplant prior to entry of the study.
* Patients must be fully recovered from all acute treatment related toxicities of all prior therapies.
* Laboratory test: adequate hematological (platelets ≥ 100x10e9/L, neutrophils ≥ 1.0x10e9/L, hemoglobin ≥ 5,6 mmol/L), renal function (creatinine \<1.5 times ULN) and liver function (≤3 times ULN) values.
* Negative pregnancy test for female participants of child-bearing potential, where child-bearing potential is defined as a fertile female who is pubertal or post-pubertal and not permanently sterile (hysterectomy, bilateral salpingectomy, bilateral oophorectomy).
* Female participants of child-bearing potential, who are sexually active, agree to use ac-ceptable birth control starting at informed consent and continuing for at least 120 days af-ter DNX-2401 administration. Male participants agree to use acceptable birth control start-ing at informed consent and continuing for at least 90 days after DNX-2401 administration.

Exclusion Criteria:

* Any medical or psychological condition or disease that might interfere with the subject's ability to participate or give informed consent (if older than 16 years).
* Spinal location, or lesions considered risky for stereotactic injection of virus or that might favor entrance of the virus in the ventricular system.
* Any treatment outside the allowable guidelines outlined in the inclusion criteria.
* Severe acute infection or intercurrent medical condition including, but not limited to se-vere renal, hepatic, heart or bone marrow failure that based on investigator discretion do not permit inclusion in the study.
* Subjects with immunodeficiency or autoimmune conditions, active hepatitis or known HIV. No testing for Hepatitis B, Hepatitis C and HIV is required unless mandated by local health authority.
* Subjects with another primary malignancy.
* Prior history of encephalitis, multiple sclerosis or other CNS infections or primary CNS dis-ease that would interfere with evaluation.
* Li Fraumeni Syndrome or a known germ line deficit in the retinoblastoma gene or its relat-ed pathways.
* Concurrent therapy with any antiviral drug or any immunosuppressive drug (except ster-oids).
* Life or life-attenuated vaccinations within 30 days prior to DNX-2401 administration and while participating in the study. Killed vaccines are permitted.
* Prior participant in experimental viral therapy.
* Inability to undergo MRI scans for any reason.
* Pregnancy or breastfeeding.