Phase 1 trial of vocimagene amiretrorepvec and 5-fluorocytosine for recurrent high-grade glioma.
Sci Transl Med
; 8(341): 341ra75, 2016 06 01.
Article
en En
| MEDLINE
| ID: mdl-27252174
ABSTRACT
Toca 511 (vocimagene amiretrorepvec) is an investigational nonlytic, retroviral replicating vector (RRV) that delivers a yeast cytosine deaminase, which converts subsequently administered courses of the investigational prodrug Toca FC (extended-release 5-fluorocytosine) into the antimetabolite 5-fluorouracil. Forty-five subjects with recurrent or progressive high-grade glioma were treated. The end points of this phase 1, open-label, ascending dose, multicenter trial included safety, efficacy, and molecular profiling; survival was compared to a matching subgroup from an external control. Overall survival for recurrent high-grade glioma was 13.6 months (95% confidence interval, 10.8 to 20.0) and was statistically improved relative to an external control (hazard ratio, 0.45; P = 0.003). Tumor samples from subjects surviving more than 52 weeks after Toca 511 delivery disproportionately displayed a survival-related mRNA expression signature, identifying a potential molecular signature that may correlate with treatment-related survival rather than being prognostic. Toca 511 and Toca FC show excellent tolerability, with RRV persisting in the tumor and RRV control systemically. The favorable assessment of Toca 511 and Toca FC supports confirmation in a randomized phase 2/3 trial (NCT02414165).
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Retroviridae
/
Vectores Genéticos
/
Glioma
Tipo de estudio:
Clinical_trials
Idioma:
En
Revista:
Sci Transl Med
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos