Intratumoral DNX-2401 for High Grade Pediatric Brain Tumors

NCT07424092 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: PED-DNX24012024-515009-24-00
• Study Type: interventional
• Target: 39
• Locations: 2 countries
• Sites: 2

Brief Summary

The goal of this clinical trial is to learn if intratumoral administration of DNX-2401 works to treat recurrent and refractory high grade brain tumors in children and young adults. It will also learn about the safety of DNX-2401. The main questions it aims to answer are:

• Does a single intratumoral administration of DNX-2401 elicit tumor response and improve survival?
• Is a single intratumoral administration of DNX-2401 safe and well tolerated? Participants will:
• Undergo surgery for tumor biopsy followed by a single intratumoral administration of DNX-2401
• Visit the clinic periodically for checkups and tests

Conditions

High Grade Glioma; Ependymoma; Embryonal Tumor of Brain; Recurrence; Refractory; Pediatric; Young Adult

Keywords

High Grade Brain Tumors; High Grade Glioma; Ependymoma; Embryonal CNS Tumors; Recurrent or refractory; Pediatric and young adult patients; Oncolytic virus; DNX-2401

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Percentage of patients achieving a Best Overall Response (BOR) of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) maintained for at least 12 weeks. Response is assessed according to the Response Assessment in Pediatric Neuro-Oncology (RAPNO) criteria.

  Up to 52 weeks post-injection.

Secondary Outcomes (8)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  From treatment administration through week 12.

• Number of Participants With Serious Adverse Events (SAEs)

  From treatment administration through week 12.

• Overall Survival (OS).

  Up to 12 months.

• Progression-Free Survival (PFS).

  Up to 12 months.

• Time to Best Overall Response

  Up to 52 weeks.

Other Outcomes (1)

• Correlative analysis

  From baseline to month 12 following DNX-2401 injection.

Study Arms (1)

Single intratumoral infusion of DNX-2401

EXPERIMENTAL

Single intratumoral infusion of 5 × 10\^10 viral particles of DNX-2401 after tumor biopsy.

Biological: DNX-2401

Interventions

DNX-2401 BIOLOGICAL

Single intratumoral infusion of 5 × 10\^10 viral particles of DNX-2401 after tumor biopsy.

Single intratumoral infusion of DNX-2401

Eligibility Criteria

• Age: 1 Year - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Clinica Universidad de Navarra, Universidad de Navarra: lead
• Princess Maxima Center for Pediatric Oncology: collaborator
• Asociación Española contra el Cáncer: collaborator

Study Sites (2)

Princess Máxima Centrum

Utrecht, 3584, Netherlands

NOT YET RECRUITING

Cancer Center Clínica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

RECRUITING

Related Publications (14)

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• Kline C, Felton E, Allen IE, Tahir P, Mueller S. Survival outcomes in pediatric recurrent high-grade glioma: results of a 20-year systematic review and meta-analysis. J Neurooncol. 2018 Mar;137(1):103-110. doi: 10.1007/s11060-017-2701-8. Epub 2017 Dec 4.

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• Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989 Mar;10(1):1-10. doi: 10.1016/0197-2456(89)90015-9.

  PMID: 2702835 BACKGROUND

• Gallego Perez-Larraya J, Garcia-Moure M, Labiano S, Patino-Garcia A, Dobbs J, Gonzalez-Huarriz M, Zalacain M, Marrodan L, Martinez-Velez N, Puigdelloses M, Laspidea V, Astigarraga I, Lopez-Ibor B, Cruz O, Oscoz Lizarbe M, Hervas-Stubbs S, Alkorta-Aranburu G, Tamayo I, Tavira B, Hernandez-Alcoceba R, Jones C, Dharmadhikari G, Ruiz-Moreno C, Stunnenberg H, Hulleman E, van der Lugt J, Idoate MA, Diez-Valle R, Esparragosa Vazquez I, Villalba M, de Andrea C, Nunez-Cordoba JM, Ewald B, Robbins J, Fueyo J, Gomez-Manzano C, Lang FF, Tejada S, Alonso MM. Oncolytic DNX-2401 Virus for Pediatric Diffuse Intrinsic Pontine Glioma. N Engl J Med. 2022 Jun 30;386(26):2471-2481. doi: 10.1056/NEJMoa2202028.

  PMID: 35767439 BACKGROUND

• Garcia-Moure M, Gonzalez-Huarriz M, Labiano S, Guruceaga E, Bandres E, Zalacain M, Marrodan L, de Andrea C, Villalba M, Martinez-Velez N, Laspidea V, Puigdelloses M, Gallego Perez-Larraya J, Inigo-Marco I, Stripecke R, Chan JA, Raabe EH, Kool M, Gomez-Manzano C, Fueyo J, Patino-Garcia A, Alonso MM. Delta-24-RGD, an Oncolytic Adenovirus, Increases Survival and Promotes Proinflammatory Immune Landscape Remodeling in Models of AT/RT and CNS-PNET. Clin Cancer Res. 2021 Mar 15;27(6):1807-1820. doi: 10.1158/1078-0432.CCR-20-3313. Epub 2020 Dec 29.

  PMID: 33376098 BACKGROUND

• Martinez-Velez N, Marigil M, Garcia-Moure M, Gonzalez-Huarriz M, Aristu JJ, Ramos-Garcia LI, Tejada S, Diez-Valle R, Patino-Garcia A, Becher OJ, Gomez-Manzano C, Fueyo J, Alonso MM. Delta-24-RGD combined with radiotherapy exerts a potent antitumor effect in diffuse intrinsic pontine glioma and pediatric high grade glioma models. Acta Neuropathol Commun. 2019 Apr 29;7(1):64. doi: 10.1186/s40478-019-0714-6.

  PMID: 31036068 BACKGROUND

• Martinez-Velez N, Garcia-Moure M, Marigil M, Gonzalez-Huarriz M, Puigdelloses M, Gallego Perez-Larraya J, Zalacain M, Marrodan L, Varela-Guruceaga M, Laspidea V, Aristu JJ, Ramos LI, Tejada-Solis S, Diez-Valle R, Jones C, Mackay A, Martinez-Climent JA, Garcia-Barchino MJ, Raabe E, Monje M, Becher OJ, Junier MP, El-Habr EA, Chneiweiss H, Aldave G, Jiang H, Fueyo J, Patino-Garcia A, Gomez-Manzano C, Alonso MM. The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models. Nat Commun. 2019 May 28;10(1):2235. doi: 10.1038/s41467-019-10043-0.

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• Nassiri F, Patil V, Yefet LS, Singh O, Liu J, Dang RMA, Yamaguchi TN, Daras M, Cloughesy TF, Colman H, Kumthekar PU, Chen CC, Aiken R, Groves MD, Ong SS, Ramakrishna R, Vogelbaum MA, Khagi S, Kaley T, Melear JM, Peereboom DM, Rodriguez A, Yankelevich M, Nair SG, Puduvalli VK, Aldape K, Gao A, Lopez-Janeiro A, de Andrea CE, Alonso MM, Boutros P, Robbins J, Mason WP, Sonabend AM, Stupp R, Fueyo J, Gomez-Manzano C, Lang FF, Zadeh G. Oncolytic DNX-2401 virotherapy plus pembrolizumab in recurrent glioblastoma: a phase 1/2 trial. Nat Med. 2023 Jun;29(6):1370-1378. doi: 10.1038/s41591-023-02347-y. Epub 2023 May 15.

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MeSH Terms

Conditions

Glioma; Ependymoma; Recurrence

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jaime Gállego Pérez de Larraya, M.D., Ph.D.

  Cancer Center Clínica Universidad de Navarra

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jaime Gállego Pérez de Larraya, M.D., Ph.D.

CONTACT

+34 948 25 54 00; jgallego@unav.es

Central Unit for Clinical Trials

CONTACT

+34 948 25 54 00; ucicec@unav.es

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study population, i.e. pediatric and young adults patients with recurrent/refractory high-grade brain tumors will be divided into three different cohorts or study groups based on diagnosis: a) high-grade gliomas, b) embryonal CNS tumors, and c) ependymomas. A Simon 2-stage optimal design will be used to maximize the probability of detecting the treatment's effectiveness. Accordingly, initially 5 patients will be first included per group. When a response in 1 out of the 5 initial patients per group is observed, inclusion in that group will be expanded until a total of 13 patients. All participants will receive a single intratumoral dose of 5 × 10\^10 viral particles of DNX-2401.

Study Record Dates

• First Submitted: February 5, 2026
• First Posted: February 20, 2026
• Study Start: May 12, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2029
• Last Updated: May 27, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: The IPD will be made available after publication of the primary results.
• Access Criteria: Access to de-identified individual participant data will be provided to qualified researchers upon reasonable request. Requests should be directed to the principal investigator.

Locations

NL (1); ES (1)