Convection Enhanced Delivery of the Oncolytic Adenovirus Delta24-RGD in Patients with Recurrent GBM: A Phase I Clinical Trial Including Correlative Studies

Erik H.P. Van Putten*, Anne Kleijn, Victor W. Van Beusechem, David Noske, Cor H.J. Lamers, Anna L. De Goede, Sander Idema, Daphna Hoefnagel, Jenneke J. Kloezeman, Juan Fueyo, Frederick F. Lang, Charlotte E. Teunissen, Rene M. Vernhout, Cathy Bakker, Winald Gerritsen, David T. Curiel, Arnold Vulto, Martine L.M. Lamfers, Clemens M.F. Dirven

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

23 Citations (Scopus)
2 Downloads (Pure)


Purpose: Testing safety of Delta24-RGD (DNX-2401), an oncolytic adenovirus, locally delivered by convection enhanced delivery (CED) in tumor and surrounding brain of patients with recurrent glioblastoma. Patients and Methods: Dose-escalation phase I study with 3+3 cohorts, dosing 107to 1 × 1011viral particles (vp) in 20 patients. Besides clinical parameters, adverse events, and radiologic findings, blood, cerebrospinal fluid (CSF), brain interstitial fluid, and excreta were sampled over time and analyzed for presence of immune response, viral replication, distribution, and shedding. Results: Of 20 enrolled patients, 19 received the oncolytic adenovirus Delta24-RGD, which was found to be safe and feasible. Four patients demonstrated tumor response on MRI, one with complete regression and still alive after 8 years. Most serious adverse events were attributed to increased intracranial pressure caused by either an inflammatory reaction responding to steroid treatment or viral meningitis being transient and self-limiting. Often viral DNA concentrations in CSF increased over time, peaking after 2 to 4 weeks and remaining up to 3 months. Concomitantly Th1- and Th2- associated cytokine levels and numbers of CD3+T and natural killer cells increased. Posttreatment tumor specimens revealed increased numbers of macrophages and CD4+and CD8+T cells. No evidence of viral shedding in excreta was observed. Conclusions: CED of Delta24-RGD not only in the tumor but also in surrounding brain is safe, induces a local inflammatory reaction, and shows promising clinical responses.

Original languageEnglish
Pages (from-to)1572-1585
Number of pages14
JournalClinical Cancer Research
Issue number8
Publication statusPublished - 15 Apr 2022

Bibliographical note

Funding Information: This project has been supported through the NCI-RAID Program of the Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, NCI, and by grants of the Dutch Cancer Society (KWF); the Netherlands Organization for Health Research and Development (ZonMw) Program Translational Gene Therapy Research; and the Erasmus MC Mrace program. We thank R. Verdijk, M.D., Ph.D., for evaluating selected pathology samples; W. van den Bossche, M.D., for the flow cytometric analysis of the re-resection tumor sample; Lisette Vogelezang and Eftichia Stavrakaki for technical assistance; and the members of the Data Safety Monitoring Board (P. Sillevis Smitt, R. Hoeben, J. Heijmans, C. Bangma, F.F. Lang). We also wish to express our gratitude and respect to the late Charles A. Conrad for his achievements in the field of oncolytic viral therapy and valuable contributions to this study.

Publisher Copyright: © 2022 American Association for Cancer Research Inc.. All rights reserved.


Dive into the research topics of 'Convection Enhanced Delivery of the Oncolytic Adenovirus Delta24-RGD in Patients with Recurrent GBM: A Phase I Clinical Trial Including Correlative Studies'. Together they form a unique fingerprint.

Cite this