Oncolytic DNX-2401 virotherapy plus pembrolizumab in recurrent glioblastoma: a phase 1/2 trial

Farshad Nassiri, Vikas Patil, Leeor S. Yefet, Olivia Singh, Jeff Liu, Rachel M.A. Dang, Takafumi N. Yamaguchi, Mariza Daras, Timothy F. Cloughesy, Howard Colman, Priya U. Kumthekar, Clark C. Chen, Robert Aiken, Morris D. Groves, Shirley S. Ong, Rohan Ramakrishna, Michael A. Vogelbaum, Simon Khagi, Thomas Kaley, Jason M. MelearDavid M. Peereboom, Analiz Rodriguez, Maxim Yankelevich, Suresh G. Nair, Vinay K. Puduvalli, Kenneth Aldape, Andrew Gao, Álvaro López-Janeiro, Carlos E. de Andrea, Marta M. Alonso, Paul Boutros, Joan Robbins, Warren P. Mason, Adam M. Sonabend, Roger Stupp, Juan Fueyo, Candelaria Gomez-Manzano, Frederick F. Lang, Gelareh Zadeh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


Immune-mediated anti-tumoral responses, elicited by oncolytic viruses and augmented with checkpoint inhibition, may be an effective treatment approach for glioblastoma. Here in this multicenter phase 1/2 study we evaluated the combination of intratumoral delivery of oncolytic virus DNX-2401 followed by intravenous anti-PD-1 antibody pembrolizumab in recurrent glioblastoma, first in a dose-escalation and then in a dose-expansion phase, in 49 patients. The primary endpoints were overall safety and objective response rate. The primary safety endpoint was met, whereas the primary efficacy endpoint was not met. There were no dose-limiting toxicities, and full dose combined treatment was well tolerated. The objective response rate was 10.4% (90% confidence interval (CI) 4.2–20.7%), which was not statistically greater than the prespecified control rate of 5%. The secondary endpoint of overall survival at 12 months was 52.7% (95% CI 40.1–69.2%), which was statistically greater than the prespecified control rate of 20%. Median overall survival was 12.5 months (10.7–13.5 months). Objective responses led to longer survival (hazard ratio 0.20, 95% CI 0.05–0.87). A total of 56.2% (95% CI 41.1–70.5%) of patients had a clinical benefit defined as stable disease or better. Three patients completed treatment with durable responses and remain alive at 45, 48 and 60 months. Exploratory mutational, gene-expression and immunophenotypic analyses revealed that the balance between immune cell infiltration and expression of checkpoint inhibitors may potentially inform on response to treatment and mechanisms of resistance. Overall, the combination of intratumoral DNX-2401 followed by pembrolizumab was safe with notable survival benefit in select patients (ClinicalTrials.gov registration: NCT02798406).

Original languageEnglish (US)
Pages (from-to)1370-1378
Number of pages9
JournalNature Medicine
Issue number6
StatePublished - Jun 2023

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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