tasadenoturev (DNX-2401) / DNAtrix - LARVOL DELTA

Oncolytic DNX-2401 Virus for Pediatric Diffuse Intrinsic Pontine Glioma. (PubMed, N Engl J Med) - P1 | "Intratumoral infusion of oncolytic virus DNX-2401 followed by radiotherapy in pediatric patients with DIPG resulted in changes in T-cell activity and a reduction in or stabilization of tumor size in some patients but was associated with adverse events. (Funded by the European Research Council under the European Union's Horizon 2020 Research and Innovation Program and others; EudraCT number, 2016-001577-33; ClinicalTrials.gov number, NCT03178032.)."

Journal • Oncolytic virus • Brain Cancer • Diffuse Intrinsic Pontine Glioma • Fatigue • Glioma • Oncology • Pain • Pediatrics • Solid Tumor

Oncolytic DNX-2401 virotherapy plus pembrolizumab in recurrent glioblastoma: a phase 1/2 trial. (PubMed, Nat Med) - P2 | "Exploratory mutational, gene-expression and immunophenotypic analyses revealed that the balance between immune cell infiltration and expression of checkpoint inhibitors may potentially inform on response to treatment and mechanisms of resistance. Overall, the combination of intratumoral DNX-2401 followed by pembrolizumab was safe with notable survival benefit in select patients (ClinicalTrials.gov registration: NCT02798406)."

IO biomarker • Journal • Oncolytic virus • P1/2 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Phase I trial of a single intratumoral injection of the oncolytic adenovirus DNX-2440 in recurrent glioblastoma (EAN 2026) - "DNX-2401, a tumour-selective oncolytic adenovirus with enhanced infectivity, has demonstrated clinical activity in adults with recurrent glioblastoma. Single intratumoral DNX-2440 administration is feasible, with a favourable safety profile and hints of antitumour activity, supporting further investigation of oncolytic virotherapy as an immunomodulatory strategy in glioblastoma."

Oncolytic virus • P1 data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

PED-DNX2401: Intratumoral DNX-2401 for High Grade Pediatric Brain Tumors (clinicaltrials.gov) - P2 | N=39 | Recruiting | Sponsor: Clinica Universidad de Navarra, Universidad de Navarra | Active, not recruiting ➔ Recruiting

Enrollment open • Brain Cancer • Embryonal Tumor • Ependymoma • Glioma • High Grade Glioma • Oncology • Pediatrics • Solid Tumor

Neurosurgical Gene Therapy: Modalities and Considerations (ASGCT 2026) - "Clinical efforts span multiple platforms, including oncolytic adenoviruses (DNX-2401), oncolytic herpes simplex virus (G47Δ), and other gene therapy platforms, each with distinct delivery requirements, immune effects, and translational challenges...This structured framework compares leading platforms and identifies translational constraints to inform platform selection and delivery optimization. Future work will expand this framework into a systematic analysis of first-in- human trials to further define neurosurgery’s role in oncolytic gene therapys."

Gene therapy • Brain Cancer • Gene Therapies • Glioma • Herpes Simplex • High Grade Glioma • Solid Tumor

PED-DNX2401: Intratumoral DNX-2401 for High Grade Pediatric Brain Tumors (clinicaltrials.gov) - P2 | N=39 | Active, not recruiting | Sponsor: Clinica Universidad de Navarra, Universidad de Navarra | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Brain Cancer • Embryonal Tumor • Ependymoma • Glioma • High Grade Glioma • Oncology • Pediatrics • Solid Tumor

PED-DNX2401: Intratumoral DNX-2401 for High Grade Pediatric Brain Tumors (clinicaltrials.gov) - P2 | N=39 | Not yet recruiting | Sponsor: Clinica Universidad de Navarra, Universidad de Navarra

Trial initiation date • Brain Cancer • Embryonal Tumor • Ependymoma • Glioma • High Grade Glioma • Oncology • Pediatrics • Solid Tumor

Treatment-related Adverse Events in Clinical Trials of Oncolytic Virus Therapies for Primary CNS Tumors: A Systematic Review (AAN 2026) - "Among individual therapies, DNX-2401 (adenovirus) had the highest total rate of severe adverse events (31/123, 25%), while G207 (HSV-1) had the highest rate of severe neurological adverse events (11/16, 69%). Conclusions Early clinical trials of oncolytic virus therapies demonstrated a tolerable safety profile, with severe adverse events occurring in only 16% of the cases. Neurological events made up nearly half of all adverse events and may warrant careful monitoring due to their higher severity rates, observed particularly in hemiparesis and cerebral edema."

Adverse events • Clinical • Oncolytic virus • Review • Brain Cancer • CNS Disorders • CNS Tumor • Epilepsy • Oncology

Assessing biomarker reproducibility for glioblastoma patient response stratification (AACR 2026) - "PAM clustering of MCP immune signatures, as reported for the DNX-2401 OV+Anti-PD1 trial, also stratified post-treatment survival in the CAN-3110 OV trial (p < 0.01), with the coldest TME subtype consistently predicting worse survival. While no individual immune signature is universally predictive in GBM immunotherapy, certain post-treatment cytokine signatures and TME stratifications are significant in multiple immunotherapy contexts, though not in standard-of-care patient cohorts. Marked spatiotemporal heterogeneity in these signatures underscores the need for composite prognostic markers resilient to sampling variance."

Biomarker • Clinical • IO biomarker • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

PED-DNX2401: Intratumoral DNX-2401 for High Grade Pediatric Brain Tumors (clinicaltrials.gov) - P2 | N=39 | Not yet recruiting | Sponsor: Clinica Universidad de Navarra, Universidad de Navarra | N=20 ➔ 39

Enrollment change • Brain Cancer • Ependymoma • Oncology • Pediatrics • Solid Tumor

INTRATUMORAL DNX-2401 ADMINISTRATION FOR RECURRENT AND REFRACTORY HIGH GRADE BRAIN TUMORS IN PEDIATRIC AND YOUNG ADULT PATIENTS (clinicaltrialsregister.eu) - P1/2 | N=20 | Not yet recruiting | Sponsor: Clinica Universidad De Navarra

New P1/2 trial • Brain Cancer • Ependymoma • Oncology • Pediatrics • Solid Tumor

Dose Ranging, Toxicity Seeking, Phase 1 Trial of Oncolytic Adenoviral Therapy for Melanoma Intracranial and Extracranial Metastases (clinicaltrials.gov) - P1 | N=50 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P1 trial • Melanoma • Oncology • Solid Tumor

PED-DNX2401: Intratumoral DNX-2401 for High Grade Pediatric Brain Tumors (clinicaltrials.gov) - P2 | N=39 | Not yet recruiting | Sponsor: Clinica Universidad de Navarra, Universidad de Navarra

New P2 trial • Brain Cancer • Embryonal Tumor • Ependymoma • Glioma • High Grade Glioma • Oncology • Pediatrics • Solid Tumor

A Decade of Oncolytic Virotherapy in Pediatric Cancers: A Systematic Review of Safety, Immune Awakening, and Emerging Efficacy. (PubMed, Cureus) - "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."

Journal • Review • Brain Cancer • CNS Tumor • Glioma • Herpes Simplex • High Grade Glioma • Oncology • Pediatrics • Solid Tumor • CD8 • IFNG • IL6

Systemic immune correlates of long-term survival after Delta-24-RGD based on the Therapeutic Adenovirus for Recurrent Glioblastoma Effect Trial (TARGET). (PubMed, Clin Cancer Res) - P1b | "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."

Journal • Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Oncology • Solid Tumor • CD8 • IFNG

Oncolytic Viruses in Glioblastoma: Clinical Progress, Mechanistic Insights, and Future Therapeutic Directions. (PubMed, Cancers (Basel)) - "Key observations include the encouraging clinical trajectory of oHSV exemplars-T-VEC (approved for melanoma) and G47Δ (approved in Japan for recurrent GBM)-the multi-center exploration of the adenovirus DNX-2401 combined with programmed death-1 (PD-1) blockade, and the early-stage status of reovirus (pelareorep) and Newcastle disease virus programs. Future directions encompass programmable vector design, optimization of systemic delivery, biomarker-guided patient selection, and rational combination immunotherapy. Collectively, OVs represent a promising immunotherapeutic strategy in GBM; further gains will hinge on vector engineering and precision combinations to translate mechanistic promise into durable clinical benefit."

IO biomarker • Journal • Review • Brain Cancer • Glioblastoma • Glioma • Herpes Simplex • High Grade Glioma • Melanoma • Oncology • Solid Tumor

Emerging therapies for glioblastoma. (PubMed, J Neurooncol) - "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."

IO biomarker • Journal • Review • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • BRAF • NTRK

Phase I trial of single intratumoral injection of DNX-2440 oncolytic adenovirus in recurrent glioblastoma patients (SNO 2025) - "DNX-2401, an oncolytic adenovirus engineered for tumor-selective replication and enhanced infectivity, has shown efficacy in adults with recurrent glioblastoma (GBM). Intratumoral DNX-2440 administration is feasible and safe, with early signs of clinical activity. These findings support the continued exploration of oncolytic virotherapy as a platform for immunomodulation and combination strategies in GBM."

Clinical • Oncolytic virus • P1 data • Brain Cancer • Glioblastoma • Immunology • Oncology • Solid Tumor

Oncolytic virotherapy: molecular mechanisms, delivery strategies, and translational insights. (PubMed, Crit Rev Oncol Hematol) - "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."

Journal • Review • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • IFNB1

Phase I trial of single intratumoral injection of DNX-2440 oncolytic adenovirus in recurrent glioblastoma patients (WFNOS 2025) - "DNX-2401, an oncolytic adenovirus engineered for tumor-selective replication and enhanced infectivity, has shown efficacy in adults with recurrent glioblastoma (GBM). Intratumoral DNX-2440 administration is feasible and safe, with early signs of clinical activity. These findings support the continued exploration of oncolytic virotherapy as a platform for immunomodulation and combination strategies in GBM."

Clinical • Oncolytic virus • P1 data • Brain Cancer • Glioblastoma • Immunology • Solid Tumor

The Emerging Role of Oncolytic Virotherapy in Glioblastoma Management. (PubMed, Cancers (Basel)) - "Despite maximal resection, radiotherapy, and temozolomide, median survival is still 12-15 months because of tumor heterogeneity, diffuse infiltration, and therapeutic resistance...Several viral backbones have advanced to clinical testing, including adenovirus (DNX-2401), herpes simplex virus (G47Δ, G207), poliovirus (PVS-RIPO), measles virus (MV-CEA), reovirus (pelareorep), vaccinia virus (Pexa-Vec), and vesicular stomatitis virus (VSV-GP)...Advances in delivery, such as convection-enhanced infusion and blood-brain barrier modulation, are also under investigation. Despite obstacles, oncolytic virotherapy holds significant potential within multimodal GBM strategies."

Journal • Review • Brain Cancer • Glioblastoma • Glioma • Herpes Simplex • High Grade Glioma • Infectious Disease • Measles • Oncology • Solid Tumor

The effect of oncolytic virotherapy on pediatric brain tumor- a systematic review. (PubMed, Childs Nerv Syst) - "OVT appears safe and feasible in pediatric brain tumors, with signals of clinical benefit in selected patients. Larger, controlled trials are needed to clarify its survival impact and define optimal therapeutic strategies."

Journal • Review • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Diffuse Intrinsic Pontine Glioma • Ependymoma • Glioblastoma • Glioma • High Grade Glioma • Oncology • Pain • Pediatrics • Solid Tumor

Assessing Nectin and Nestin Expression in Diffuse Midline Gliomas: A Step Toward HSV-Based Oncolytic Viral Immunotherapy (USCAP 2025) - P1 | "Additionally, the oncolytic adenovirus DNX-2401 has shown promising results in treating diffuse intrinsic pontine gliomas (DIPG), a subset of DMGs, in pediatric patients (NCT03178032). The co-expression of Nectin and Nestin in DMGs is significant, as it suggests that these tumors may be suitable candidates for CAN-3110 oncolytic immunotherapy. Further studies are needed to explore the therapeutic potential and clinical application of this approach in DMGs."

IO biomarker • Oncolytic virus • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioblastoma • Glioma • Malignant Glioma • Oncology • Pediatrics • Solid Tumor • NES

Efficacy of Oncolytic Viral Therapy in Pediatric Brain Tumors: A Systematic Review of Clinical Trials (AAN 2025) - "The virus agents used in studied were HSV G-207, DNX-2401, and ADV-tk...The majority of patients underwent additional treatments, including radiotherapy, surgery and chemotherapy, with temozolomide and lomustine being the most frequently used chemotherapeutic agents...Early-phase trials suggest that oncolytic virotherapy is generally well-tolerated and shows potential efficacy especially if it used as an adjuvant therapy along with chemotherapy, radiotherapy or surgery. However, larger and more advanced clinical trials are required to determine survival rates, adverse effects and make definitive comparisons with conventional therapeutic approach."

Clinical • IO biomarker • Oncolytic virus • Review • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Ependymoma • Glioblastoma • Glioma • Hepatocellular Cancer • Hepatology • Malignant Glioma • Melanoma • Oncology • Pain • Pancreatic Cancer • Pediatrics • Solid Tumor

A viral attack on brain tumors: the potential of oncolytic virus therapy. (PubMed, J Neurovirol) - "Furthermore, the discovery and creation of new OVs that can seamlessly integrate gene therapy strategies, such as cytotoxic, anti-angiogenic, and immunostimulatory, are promising advancements. This review presents an overview of the latest advancements in OVs transduction for brain cancer, focusing on the safety and effectiveness of G207, G47Δ, M032, rQNestin34.5v.2, C134, DNX-2401, Ad-TD-nsIL12, NSC-CRAd-S-p7, TG6002, and PVSRIPO. These are evaluated in both preclinical and clinical models of various brain tumors."

Journal • Oncolytic virus • Review • Brain Cancer • Gene Therapies • Oncology • Solid Tumor