CTNI-47. PHASE I TRIAL OF SINGLE INTRATUMORAL INJECTION OF DNX-2440 ONCOLYTIC ADENOVIRUS IN RECURRENT GLIOBLASTOMA PATIENTS

Abstract BACKGROUND Oncolytic immunovirotherapy is emerging as a potential therapeutic strategy in neuro-oncology. DNX-2401, an oncolytic adenovirus engineered for tumor-selective replication and enhanced infectivity, has shown efficacy in adults with recurrent glioblastoma (GBM). DNX-2440 builds on this platform by incorporating the OX40 ligand to enhance antitumor immunity through T cell co-stimulation and modulation of the immunosuppressive tumor microenvironment. METHODS We conducted an open-label single-center phase I study to evaluate the safety and preliminary efficacy of a single intratumoral injection of DNX-2440 in patients with first or second GBM recurrence. This 3 + 3 dose-escalation trial evaluated an initial dose of 4×10⁹ viral particles (vp) and a target dose of 4×10¹⁰ vp. Eligible patients had a single measurable lesion ≥10 mm in two perpendicular diameters and ≤25 cc in volume. All patients underwent stereotactic biopsy followed by intratumoral virus injection.[j1] RESULTS Sixteen patients (6 female [37.5%], 10 male [62.5%]) with a median age of 55 years (range, 39-80) and a median Karnofsky Performance Status of 80 (range, 70-90) were enrolled. No dose-limiting toxicities were observed during the escalation phase (3 patients at 4×10⁹ vp; 3 at 4×10¹⁰ vp). The remaining patients received 4×10¹⁰ vp in the expansion cohort. DNX-2440 was well tolerated, with no serious adverse events attributed to the treatment. Clinical benefit, including tumor reduction and prolonged survival, was observed in three patients. Correlative analyses to assess systemic immune responses and characterize the tumor immune microenvironment were performed to better understand the viral therapeutic effect. CONCLUSION 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.