RT Journal Article
T1 A phase 1 dose escalation study of the oncolytic adenovirus enadenotucirev, administered intravenously to patients with epithelial solid tumors (EVOLVE)
A1 Machiels, Jean-Pascal
A1 Salazar, Ramón
A1 Rottey, Sylvie
A1 Duran, Ignacio
A1 Dirix, Luc
A1 Geboes, Karen
A1 Wilkinson-Blanc, Christine
A1 Pover, Gillian
A1 Alvis, Simon
A1 Champion, Brian
A1 Fisher, Kerry
A1 McElwaine-John, Hilary
A1 Beadle, John
A1 Calvo, Emiiano
K1 Clinical Trials
K1 Pharmacokinetics and pharmacodynamics
K1 Enadenotucirev
K1 Oncolytic adenovirus
K1 Epithelial solid tumor
K1 Intravenous
K1 Farmacocinética
K1 Farmacología
K1 Ensayos clínicos como asunto
K1 Adenoviridae
K1 Carcinoma
K1 Inyecciones intravenosas
AB 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 × 1010 and 1 × 1013 viral particles (vp) on days 1, 3, and 5 (single cycle) was used to determine an appropriate MTD. Subsequent treatment cohorts (phase 1a, n = 6 and phase 1b, n = 24) examined the feasibility of repeated dosing cycles in either 3-weekly or weekly dosing regimens.Results: Enadenotucirev displayed a predictable and manageable safety profile at doses up to the MTD of 3 × 1012 vp, irrespective of infusion time or dosing schedule. The most commonly reported treatment-emergent adverse events (TEAEs) of grade 3 or higher were hypoxia, lymphopenia, and neutropenia. The frequency of all TEAEs (notably pyrexia and chills) was highest within 24 h of the first enadenotucirev infusion and decreased upon subsequent dosing. Additionally, delivery of three doses of enadenotucirev over 5 days optimized pharmacokinetic and chemokine profiles in the circulation over time.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 × 1012 vp.
PB BioMed Central Ltd
YR 2019
FD 2019-01-28
LK http://hdl.handle.net/10668/3170
UL http://hdl.handle.net/10668/3170
LA en
NO Machiels JP, Salazar R, Rottey S, Duran I, Dirix L, Geboes K, et al. A phase 1 dose escalation study of the oncolytic adenovirus enadenotucirev, administered intravenously to patients with epithelial solid tumors (EVOLVE). J Immunother Cancer. 2019 Jan 28;7(1):20.
NO Artículo editado por BMC en 2019. La revista "Journal for ImmunoTherapy of Cancer" pasa a ser propiedad de BMJ en 2020, quien actualmente la edita y distribuye.
DS RISalud
RD Apr 9, 2025