Results of A Phase 1 study of the oncolytic adenovirus DNX-2401 with radiotherapy for newly diagnosed diffuse intrinsic pontine glioma (DIPG)
Ikusi/ Ireki
Data
2021-06-01Egilea
García Moure, Marc
Gállego Pérez de Larraya, Jaime
Patiño García, Ana
González Huarriz, Marisol
Jones, Chris
MacKay, Alan
Van der Lugt, Jasper
Hulleman, Esther
De Andrea, Carlos
Astigarraga Aguirre, María Iciar
García Ariza, Miguel Angel
López Ibor, Blanca
Villalba, María
Lang, Frederick F.
Fueyo, Juan
Gómez Manzano, Candelaria
Dobbs, Jessica
Díez Valle, Ricardo
Alonso, Marta M.
Tejada, Sonia
Neuro-Oncology 23(1) : (2021) // Article ID i47
Laburpena
Background
A Phase 1, single center study is ongoing to evaluate the conditionally replicative oncolytic adenovirus, DNX-2401 (tasadenoturev), followed by radiotherapy (RT) in pediatric patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG).
Methods
Patients 1–18 years with newly diagnosed DIPG with no prior treatment, Lansky/Karnofsky performance score ≥ 70, and adequate organ function were enrolled. A tumor biopsy was performed followed by a single intratumoral injection of 1e10-5e10 virus particles (vp) DNX-2401. Conventional radiotherapy was initiated within 1 month of DNX-2401 administration.
Results
Enrolled subjects (n=12) had a median age of 9 (range 3–18) and performance scores of 90–100 (n=4; 33%) or 70–80 (n=8; 67%). As part of a dose escalation design, subjects were treated with 1e10 vp (n=4) or 5e10 vp DNX-2401 (n=8), which was then followed by standard RT in 11 of 12 subjects (92%). No dose-limiting toxicities were observed and the treatment regimen was well-tolerated. Adverse events (AEs) have been primarily mild to moderate and consistent with underlying disease. The most commonly reported AEs (≥ 5 subjects), regardless of study drug relationship, include headache, asthenia, vomiting, anemia, leukocytosis, and fever. Two SAEs have been reported including grade 3 lymphopenia and grade 3 abdominal pain. Tumor reductions have been observed and efficacy evaluations are ongoing. As of 09Dec2020, 12-month survival (OS-12) was 71% and 4 of 12 patients had survived > 20 months. Four subjects continue to be followed for survival. Correlative analysis of tumor biopsy and peripheral samples is ongoing.
Conclusions
DNX-2401 followed by RT can be safely administered to pediatric subjects with newly diagnosed DIPG; clinical activity and preliminary survival are encouraging.