Phase 1b open-label randomized study of the oncolytic adenovirus DNX-2401 administered with or without interferon gamma for recurrent glioblastoma.

Abstract

2002 Background: DNX-2401 is a replication-competent, tumor-selective, oncolytic adenovirus with enhanced infectivity that causes durable tumor control by killing tumor cells and eliciting antitumor immunity. To increase immune activation, a phase 1b randomized study of intratumoral DNX-2401 alone versus DNX-2401 with interferon gamma (IFN) was conducted. Methods: A total of 27 patients with biopsy-confirmed glioblastoma at first or second recurrence received a single intratumoral injection of 3e10 vp DNX-2401. Patients were randomized in a 2:1 ratio to receive 50 mcg/m2 of subcutaneous IFN (Actimmune) Q3W initiated 14 days after DNX-2401 or to be followed without further treatment for safety and survival. Results: Twenty-seven (27) patients were enrolled following first (59%) or second (41%) recurrence having previously failed surgery, radiation, and temozolomide (100%). The median longest tumor diameter was 40 mm (range 20-77 mm). Patients were randomized to DNX-2401 followed by IFN (n = 18) or to DNX-2401 alone (n = 9). Due to the poor tolerability of IFN, the median duration of treatment was only 6 weeks (range 0-30 weeks), and two patients did not initiate treatment as scheduled due to early clinical deterioration. The most frequent grade 3-4 AEs across treatment groups were fatigue, headache, and seizures consistent with pre-existing symptoms, underlying disease and/or surgery. Based upon a preliminary intent-to-treat analysis, IFN did not appear to provide additional benefit. However, OS-12 and OS-18 for all patients enrolled was 33% and 22%, respectively regardless of treatment assignment. Three patients remain alive at 19, 21, and 22 months (DNX-2401, n = 1; DNX-2401 + IFN, n = 2). Interestingly, 50% of patients with a baseline tumor diameter of ≤ 42 mm survived beyond 12 months, potentially identifying a sub-population of patients that may live longer following intratumoral DNX-2401. Conclusions: DNX-2401 was well tolerated as monotherapy. Although the addition of IFN did not improve survival, clinical activity following a single injection of DNX-2401 is encouraging and supports an ongoing Phase II study of DNX-2401 for recurrent glioblastoma. Clinical trial information: NCT02197169.