tasadenoturev (DNX-2401)

P2, N=39, Recruiting, Clinica Universidad de Navarra, Universidad de Navarra | Active, not recruiting --> Recruiting

P2, N=39, Active, not recruiting, Clinica Universidad de Navarra, Universidad de Navarra | Not yet recruiting --> Active, not recruiting

P2, N=39, Not yet recruiting, Clinica Universidad de Navarra, Universidad de Navarra

P2, N=39, Not yet recruiting, Clinica Universidad de Navarra, Universidad de Navarra | N=20 --> 39

P1/2, N=20, Not yet recruiting, Clinica Universidad De Navarra

P1, N=50, Not yet recruiting, M.D. Anderson Cancer Center

P2, N=39, Not yet recruiting, Clinica Universidad de Navarra, Universidad de Navarra

Investigated viral platforms included herpes simplex virus type 1 (G207, HSV1716), adenovirus (DNX-2401, ICOVIR-5, Ad-TD-nsIL12), T-VEC (HSV-1), poliovirus (PVSRIPO), Seneca Valley virus, and reovirus. Overall risk of bias was moderate, while the certainty of evidence was rated as low for safety outcomes and very low for efficacy. These findings indicate that oncolytic virotherapy is safe, feasible, and biologically active in children with malignant brain and solid tumors, and that preliminary survival signals and consistent immune activation support further investigation through larger, multicenter randomized trials and combination strategies with radiotherapy or immune checkpoint inhibitors.

Immunological fitness, assessed by an anti-adenoviral specific antibody response and higher levels of activated CD8+ NKT-like cells after Delta-24-RGD treatment, may have utility as an early surrogate of a robust systemic immune response that correlates with long-term survival.

Glioblastoma (GBM) remains associated with poor outcomes, with a median survival of 15-18 months despite maximal safe resection, radiotherapy, and temozolomide. CAR T-cell therapies are advancing toward bispecific and armored constructs with locoregional delivery, while oncolytic viruses such as DNX-2401 and PVSRIPO demonstrate potential for durable responses in select patients. Looking ahead, progress is likely to arise from biomarker-informed, multimodal regimens that integrate targeted agents, next-generation immunotherapies, and precision-guided strategies, while embedding translational endpoints into trial design to address the complex biology and therapeutic resistance of GBM.

We highlight trials where OVs prime checkpoint response (e.g., DNX-2401→pembrolizumab in recurrent glioblastoma) and where vector design (e.g., TK-deleted vaccinia, CG0070) or payloads (e.g., IFNβ, NIS) drive measurable benefit. We conclude with actionable priorities, patient selection by IFN-pathway competence, receptor-tropism panels, and rational OV-ICI sequencing, to accelerate durable responses.

P1, N=36, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Sep 2023 --> Sep 2027 | Trial primary completion date: Sep 2023 --> Sep 2027