Intratumoral DNX-2401 Administration for Recurrent and Refractory High Grade Brain Tumors in Pediatric and Young Adult Patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Clinica Universidad De Navarra

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

8 May 2026 → ongoing

Decision date (initial)

2026-03-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Private donors · CV Bio · Prinses Máxima Centrum · AECC · University Clinic of Navarra

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To determine if single intratumoral administration of DNX-2401 in recommended phase II dose of 5x10¹⁰ viral particles elicits tumor response in children with recurrent/refractory high grade brain tumors.

Secondary objectives 5

1. To assess the safety and tolerability of intratumoral administration of DNX2401 as monotherapy in pediatric patients and young adults with recurrent/refractory high grade brain tumors (high grade gliomas, ependymomas and embryonal tumors).
2. To assess time to best response.
3. To assess progression free survival (PFS) and overall survival (OS) in months and percentage after 6 and 12 months.
4. To assess changes in functional status and in quality of life (QoL).
5. To assess duration of response (DOR).

Conditions and MedDRA coding

High grade malignant brain neoplasm

Regulatory references

Scientific advice from competent authorities

Spanish Agency Of Medicines And Medical Devices

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. The participant or participant’s parents or legally acceptable representatives (if applicable) provides written informed consent for the trial and the pediatric participant provides written assent, where applicable, based on age and country requirements.
2. 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 follow-up, in whom gross total resection is not feasible, and with a life expectancy of at least 16 weeks at the time of consent.
3. 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 radiation therapy, or if there is clear histopathological confirmation of tumor recurrence.
4. Male and female participants age ≥ 1 years and ≤ 25 years.
5. 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.
6. Lansky Performance Status (LPS) ≥ 60 for participants < 16 years, or Karnofsky Performance Status (KPS) ≥ 60 for participants ≥ 16 years.
7. No other chemotherapy or immunotherapy in the 4 weeks before inclusion.
8. Steroids: free off or requiring decreasing or stable corticosteroid dose (≥ 0.05 mg/kg dexamethasone daily, or equivalent for other steroids) in the 2 weeks before DNX-2401 administration.
9. Radiation: no craniospinal irradiation, total body irradiation nor focal irradiation in the 6 weeks before inclusion.
10. Autologous Stem Cell Transplantation: patients must be ≥ 3 months post-transplant prior to entry of the study.
11. Patients must be fully recovered from all acute treatment related toxicities of all prior therapies.
12. Laboratory test: adequate hematological (platelets ≥ 100x10⁹/L, neutrophils ≥ 1.0x10⁹/L, hemoglobin ≥ 5,6 mmol/L), renal function (creatinine <1.5 times ULN) and liver function (≤3 times ULN) values.
13. 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).
14. Female participants of child-bearing potential, who are sexually active, agree to use acceptable birth control starting at informed consent and continuing for at least 120 days after DNX-2401 administration. Male participants agree to use acceptable birth control starting at informed consent and continuing for at least 90 days after DNX-2401 administration.

Exclusion criteria 13

1. 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).
2. Spinal location, or lesions considered risky for stereotactic injection of virus or that might favor entrance of the virus in the ventricular system.
3. Any treatment outside the allowable guidelines outlined in the inclusion criteria.
4. Severe acute infection or intercurrent medical condition including, but not limited to severe renal, hepatic, heart or bone marrow failure that based on investigator discretion do not permit inclusion in the study.
5. 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.
6. Subjects with another primary malignancy.
7. Prior history of encephalitis, multiple sclerosis or other CNS infections or primary CNS disease that would interfere with evaluation.
8. Li-Fraumeni Syndrome or a known germ line deficit in the retinoblastoma gene or its related pathways.
9. Concurrent therapy with any antiviral drug or any immunosuppressive drug (except steroids).
10. Life or life-attenuated vaccinations within 30 days prior to DNX-2401 administration and while participating in the study. Killed vaccines are permitted.
11. Prior participant in experimental viral therapy.
12. Inability to undergo MRI scans for any reason.
13. Pregnancy or breastfeeding.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall response rate (ORR), defined as the percentage of patients with complete response (CR), partial response (PR), or stable disease (SD for at least 12 weeks) as best response according to RAPNO criteria.

Secondary endpoints 5

1. Number of AEs and SAEs per NCI-CTCAE criteria in first 12 weeks after DNX-2401 administration.
2. Time to response.
3. Duration of response.
4. PFS, OS: 6- and 12- month PFS and OS rates.
5. LPS/KPS and QoL (PedsQL™ Generic Score Scale) parameters compared to baseline.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Clinica Universidad De Navarra

Sponsor organisation

Clinica Universidad De Navarra

Address

Avenue Pio XII 36

City

Pamplona

Postcode

31008

Country

Spain

Scientific contact point

Organisation

Clinica Universidad De Navarra

Contact name

Jaime Gallego Pérez de Larraya

Public contact point

Organisation

Clinica Universidad De Navarra

Contact name

UCEC

Locations

2 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications