ATIM-30. PHASE 1B OPEN-LABEL RANDOMIZED STUDY OF THE ONCOLYTIC VIRUS DNX-2401 ADMINISTERED WITH OR WITHOUT INTERFERON GAMMA FOR RECURRENT GLIOBLASTOMA

Abstract

BACKGROUND: DNX‐2401 is a conditionally replicative oncolytic adenovirus that causes durable tumor destruction by killing tumor cells and eliciting antitumor immunity for a period of weeks to months. OBJECTIVES. To investigate the safety, overall response rate, overall survival (OS) and quality of life of intratumoral DNX‐2401 alone versus DNX‐2401 with gamma IFN. METHOD: A total of 36 evaluable (i.e., remain on‐study 4+ weeks) patients with glioblastoma at first or second relapse are planned to receive a single intratumoral injection of 3e10vp DNX‐2401. All patients were subsequently randomized at a 2:1 ratio to receive 50 mcg/m2of subcutaneous interferon gamma (gIFN [Actimmune]) x3/week 14 days after DNX‐2401 and followed at regular intervals for adverse events, quality of life, tumor response and survival. RESULTS: Twenty‐five (25) evaluable patients were treated with 3e10vp DNX‐2401 (16 patients DNX‐2401/gIFN:9 patients DNX‐2401), in addition to a monotherapy subset (8 patients to date) who received 5e10vp of intratumoral DNX‐2401 by a proprietary cannula designed to optimize delivery of virus to brain tumors. The most frequent grade 3‐4 AEs across treatment groups were fatigue, headache, and seizures, all consistent and expected according to pre‐existing symptoms and underlying disease, surgical procedure, and concomitant use of steroids and anticonvulsants. The cannula device has been well tolerated, and imaging evidence demonstrates efficient and targeted intratumoral delivery. Preliminary OS‐12 for all patients is 39%. CONCLUSIONS: The evaluation of safety, quality of life, efficacy, and brain delivery is ongoing. Early results are promising and support a similar design of a Phase II study of DNX‐2401 with asequential pembrolizumab (Keytruda) in recurrent glioblastoma.