Background: Oncolytic immunovirotherapy is emerging as a potential therapeutic approach in neuro-oncology. The oncolytic adenovirus DNX-2401, genetically engineered for selective replication and enhanced infectivity in tumor cells, has shown efficacy in adult patients with recurrent glioblastoma. To overcome the immunosuppressive tumor microenvironment and enhance its antiglioma effect, DNX-2440 is similar virus which additionally incorporates OX40L to induce its expression in tumor cells and so increase antitumor immune response.

Material and Methods: We conducted a dose escalation phase I trial to investigate safety and efficacy of single intratumoral injection of DNX-2440 in patients with recurrent glioblastoma.

Results: 16 patients (6 female, 10 male) were enrolled and treated with DNX-2401. Median age was 55 years (39-80) and median KPS 80 (70-90). Surgery consisted of biopsy in all patients followed by intratumoral injection of DNX-2440. No dose limiting toxicity were registered during the dose escalation phase. Safety profile was acceptable with no serious adverse events related to DNX-2440 reported to date. Clinical benefit with tumor size reduction and prolonged survival have been seen in 3 patients. Correlative analyses evaluating immune response in blood samples will be conducted.

Conclusion: Our current data suggest that intratumoral injection of DNX-2440 is feasible and safe, and might provide clinical benefit in some patients with recurrent glioblastoma. Furthermore, this trial illustrates the potential of oncolytic virus platforms to reshape the brain-tumor microenvironment and its interesting role in combination strategies with other immune-oncology agents for treating this disease.