A Phase 2 interventional study of DNX-2401 in High Grade Glioma, Ependymoma and Embryonal Tumor of Brain, sponsored by Clinica Universidad de Navarra, Universidad de Navarra. Recruiting at 2 sites in 2 countries. Open to participants aged 1 Year to 25 Years. Per ClinicalTrials.gov, last updated 2026-05-27.
Sponsored by Clinica Universidad de Navarra, Universidad de Navarra · Phase 2, Interventional, and Treatment
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:
Participants will:
Tumors of the central nervous system (CNS) represent approximately 20% of childhood cancers and are the leading cause of cancer-related mortality in children. Pediatric high-grade CNS tumors, including gliomas, ependymomas and embryonal CNS tumors (such as medulloblastomas, atypical teratoid/rhabdoid tumors [AT/RT], and embryonal tumors with multilayered rosettes [ETMR]), are associated with a particularly poor prognosis, with median survival after diagnosis often below two years. Despite current conventional treatments, the outcome has not improved, and significant morbidity with impaired quality of life is frequent in survivors. This scenario is even more discouraging at the time of tumor recurrence, where curative options are nonexistent. Therefore, there is a clear need to find novel and alternative therapeutic approaches to improve both survival and quality of life of these children.
In the past years, oncolytic virotherapy has emerged as a promising therapeutic strategy, as it replicates in and destroys only tumor cells while activating the patient's immune system. Among the described oncolytic viruses, DNX-2401, a genetically modified adenovirus type 5, has shown an excellent therapeutic effect in murine models of pediatric high-grade brain tumors, as well as in children with newly diagnosed DIPG. Preclinical studies have demonstrated that Delta-24-RGD, both alone and in combination with radiotherapy, is safe and results in a significant increase in survival in immunodeficient and immunocompetent murine models of pediatric high-grade gliomas, including DIPGs. Moreover, this therapeutic benefit was also validated in AT/RT and other embryonal CNS tumors, resulting in 70% of long-term survivors and a reduction in the dissemination of these tumors. In the clinical setting, intratumoral administration of DNX-2401 has demonstrated to be safe and effective in several phase 1 and 2 clinical trials in adult patients with recurrent high-grade gliomas, both alone and with pembrolizumab, and in children with newly diagnosed DIPG in combination with radiotherapy.
This is an open-label phase 2 trial for pediatric and young adults patients, aged 1 to 25 years old, with three different types of high-grade brain tumors (high-grade gliomas including Diffuse Midline Gliomas, embryonal CNS tumors, and ependymomas), who have relapsed (i.e., tumors that return after treatment) or are refractory (i.e., do not respond to conventional treatment).
A Simon 2-stage optimal design will be used to maximize the probability of detecting the treatment's effectiveness, reducing the probability of continuing with it if it is not effective in the first stage. This statistical methodology will allow testing the null hypothesis that the true response rate is ≤20% versus the alternative hypothesis that the true response rate is ≥50%. A sample size of 13 patients per study group will be predetermined. A response (defined as complete response, partial response, or stable disease for at least 12 weeks) in at least 1 of 5 patients per study group in the first stage will be required for the study to be expanded to the second stage, and a response in 5 of 13 patients will be required to consider the treatment statistically positive.
The study participants will receive a single intratumoral dose of 5 x 10\^10 viral particles of DNX-2401 in 1 mL of 0.9% sodium chloride, administered in the brain parenchyma via a SmartFlow Neuro Ventricular Cannula (ClearPoint Neuro) with neuronavigation guidance at a controlled rate over approximately 1 hour (67 minutes at a rate of 0.90 mL/hour). Before virus delivery, a stereotactic biopsy will be performed to obtain tumor tissue.
Clinical follow-up, including neurological examination, functional status and quality of life assessment will be performed at day 3 and during clinical visits at weeks 2, 4, 8, 12, 20, 28, 40 and 52 following DNX-2401 injection. Adverse events will be recorded using the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5 tool for the first 12 weeks after experimental therapy. Postoperative MRI will be performed in all patients within 72 hours after surgery to detect the biopsy region and the DNX-2401 injection site. In the case of the preoperative Magnetic Resonnace Imaging (MRI), it will be considered the baseline MRI for response assessment, except in patients undergoing debulking surgery, in which early postoperative MRI will be considered the baseline MRI. Follow-up MRI will be performed at weeks 4, 8, 12, 20, 28, 40 and 52 following DNX-2401 injection.
Apart from the overall response rate, the treatment efficacy will also be measured in terms of survival, specifically using the following metrics: progression free survival (PFS) and overall survival (OS). PFS will be defined as the time from treatment to disease progression, determined either clinically or radiologically. OS will be defined as the time from treatment to patient death. Rates of PFS at 6- and 12-months will also be assessed as measures of outcome.
Tumor samples will be analyzed to characterize the immune tumor microenvironment and molecular composition. Blood, cerebrospinal fluid (when available), and microbiome samples will be collected longitudinally during follow-up visits to characterize viral kinetics and immune responses before and after DNX-2401 administration, and to explore correlations with clinical outcomes.
Exclusion Criteria:
Single intratumoral infusion of 5 × 10\^10 viral particles of DNX-2401 after tumor biopsy.
Biological: DNX-2401
Single intratumoral infusion of 5 × 10\^10 viral particles of DNX-2401 after tumor biopsy.
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.
Time frame: Up to 52 weeks post-injection.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Number of participants with adverse events (AEs) as a measure of safety and tolerability. All AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE).
Time frame: From treatment administration through week 12.
Number of Participants With Serious Adverse Events (SAEs)
Number of participants with serious adverse events (SAEs) potentially related to DNX-2401.
Time frame: From treatment administration through week 12.
Overall Survival (OS).
Time from treatment administration to death from any cause.
Time frame: Up to 12 months.
Progression-Free Survival (PFS).
Time from treatment administration to the first documentation of objective tumor progression or death from any cause.
Time frame: Up to 12 months.
Time to Best Overall Response
Time from the date of DNX-2401 administration to the first documentation of the best objective response (Complete Response \[CR\], Partial Response \[PR\], or Stable Disease \[SD\] maintained for at least 12 weeks) according to RAPNO criteria.
Time frame: Up to 52 weeks.
Duration of Overall Response
Time from the first documentation of objective response (CR, PR, or SD) to the first documentation of objective tumor progression (according to RAPNO criteria) or death from any cause.
Time frame: From the date of first documented response up to 52 weeks.
Change From Baseline in Performance Status (Karnofsky/Lansky Score)
Performance status will be assessed using the Karnofsky Performance Scale (for patients aged 16 years and older) or the Lansky Performance Scale (for patients younger than 16 years). Both scales range from 0 to 100, where 0 represents death and 100 represents normal activity. Higher scores indicate better functional status.
Time frame: Baseline and weeks 2, 4, 8, 12, 20, 28, 40 and 52 following DNX-2401 injection.
Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Generic Core Scale Total Score.
The PedsQL Generic Core Scale is a 23-item instrument. Each item is reversed-scored and linearly transformed to a 0-100 scale (0=100, 1=75, 2=50, 3=25, 4=0). The total score is the sum of all items divided by the number of items answered. The total score ranges from 0 to 100, where 0 indicates poor quality of life and 100 indicates better quality of life.
Time frame: Baseline and weeks 2, 4, 8, 12, 20, 28, 40 and 52 following DNX-2401 injection.
Correlative analysis
To characterize the tumor immune microenvironment and molecular composition, the viral kinetics, the immune response to the treatment, and the fecal microbioma before and after DNX-2401 administration. Tumor samples and sequential blood and fecal samples (as well as cerebrospinal fluid samples, when available) will be analyzed, and correlated with clinical otucomes.
Time frame: From baseline to month 12 following DNX-2401 injection.
Plan to share: Yes — De-identified individual participant data that underlie the results reported in publications arising from this study will be shared with qualified researchers or study collaborators.
Supporting information: Study protocol
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Clinica Universidad de Navarra, Universidad de Navarra