A phase 1 dose escalation study of the oncolytic adenovirus enadenotucirev, administered intravenously to patients with epithelial solid tumors (EVOLVE).
Clinical trials
Enadenotucirev
Epithelial solid tumor
Intravenous
Oncolytic adenovirus
Pharmacokinetics and pharmacodynamics
Journal
Journal for immunotherapy of cancer
ISSN: 2051-1426
Titre abrégé: J Immunother Cancer
Pays: England
ID NLM: 101620585
Informations de publication
Date de publication:
28 01 2019
28 01 2019
Historique:
received:
31
07
2018
accepted:
13
01
2019
entrez:
30
1
2019
pubmed:
30
1
2019
medline:
2
4
2020
Statut:
epublish
Résumé
Enadenotucirev is a chimeric adenovirus with demonstrated preclinical tumor-selective cytotoxicity and a short half-life. Further clinical mechanism of action data showed that enadenotucirev can gain access to and replicate within different types of epithelial tumors. This phase 1 dose escalation study assessed intravenous (IV) dose escalation with enadenotucirev to establish the maximum tolerated dose (MTD) and subsequently identify a suitable schedule for repeated cycles. Sixty-one patients with advanced epithelial tumors unresponsive to conventional therapy were enrolled and received enadenotucirev monotherapy as part of this study. During the phase 1a dose escalation (n = 22) and expansion (n = 9), delivery of enadenotucirev between 1 × 10 Enadenotucirev displayed a predictable and manageable safety profile at doses up to the MTD of 3 × 10 This study provides key clinical data in patients with solid epithelial tumors following treatment with IV enadenotucirev monotherapy and supports further investigation of enadenotucirev in combination with other therapeutic agents at doses up to the MTD of 3 × 10 ( ClinicalTrials.gov Identifier: NCT02028442 ). Trial registration date: 07 January 2014 - Retrospectively registered.
Sections du résumé
BACKGROUND
Enadenotucirev is a chimeric adenovirus with demonstrated preclinical tumor-selective cytotoxicity and a short half-life. Further clinical mechanism of action data showed that enadenotucirev can gain access to and replicate within different types of epithelial tumors. This phase 1 dose escalation study assessed intravenous (IV) dose escalation with enadenotucirev to establish the maximum tolerated dose (MTD) and subsequently identify a suitable schedule for repeated cycles.
METHODS
Sixty-one patients with advanced epithelial tumors unresponsive to conventional therapy were enrolled and received enadenotucirev monotherapy as part of this study. During the phase 1a dose escalation (n = 22) and expansion (n = 9), delivery of enadenotucirev between 1 × 10
RESULTS
Enadenotucirev displayed a predictable and manageable safety profile at doses up to the MTD of 3 × 10
CONCLUSIONS
This study provides key clinical data in patients with solid epithelial tumors following treatment with IV enadenotucirev monotherapy and supports further investigation of enadenotucirev in combination with other therapeutic agents at doses up to the MTD of 3 × 10
TRIAL REGISTRATION
( ClinicalTrials.gov Identifier: NCT02028442 ). Trial registration date: 07 January 2014 - Retrospectively registered.
Identifiants
pubmed: 30691536
doi: 10.1186/s40425-019-0510-7
pii: 10.1186/s40425-019-0510-7
pmc: PMC6348630
doi:
Substances chimiques
Cytokines
0
enadenotucirev
0
Banques de données
ClinicalTrials.gov
['NCT02028442']
Types de publication
Clinical Trial, Phase I
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
20Commentaires et corrections
Type : CommentIn
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