Oncolytic DNX-2401 virotherapy plus pembrolizumab in recurrent glioblastoma: a phase 1/2 trial
Rattachement africain : ca, us, es, gb. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
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).
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Oncolytic DNX-2401 virotherapy plus pembrolizumab in recurrent glioblastoma: a phase 1/2 trial
- Date Crossref
- 15/05/2023
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
University Health Network Princess Margaret Cancer Center pays non établi dans la noticeÉtablissement de santé
-
University of Toronto Division of Neurosurgery pays non établi dans la noticeUniversité ou école supérieure
-
Princess Margaret Cancer Centre pays non établi dans la noticeÉtablissement de santé
-
University of California Department of Human Genetics pays non établi dans la noticeUniversité ou école supérieure
-
University of Utah Huntsman Cancer Institute and Department of Neurosurgery pays non établi dans la noticeUniversité ou école supérieure
-
Huntsman Cancer Institute pays non établi dans la noticeÉtablissement de santé
-
Northwestern University Department of Neurology pays non établi dans la noticeUniversité ou école supérieure
-
University of Minnesota Department of Neurosurgery pays non établi dans la noticeUniversité ou école supérieure
-
The State University of New Jersey Rutgers pays non établi dans la noticeUniversité ou école supérieure
-
Texas Oncology pays non établi dans la noticeStructure de recherche
-
The Ohio State University Wexner Medical Center Department of Neurology pays non établi dans la noticeÉtablissement de santé
-
NewYork–Presbyterian Hospital pays non établi dans la noticeÉtablissement de santé
Princess Margaret Cancer Center — University Health Network, Division of Neurosurgery — University of Toronto et Princess Margaret Cancer Centre, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.