TY - JOUR
T1 - Phase 1 trial of vocimagene amiretrorepvec and 5-fluorocytosine for recurrent high-grade glioma
AU - Cloughesy, Timothy F.
AU - Landolfi, Joseph
AU - Hogan, Daniel J.
AU - Bloomfield, Stephen
AU - Carter, Bob
AU - Chen, Clark C.
AU - Elder, J. Bradley
AU - Kalkanis, Steven N.
AU - Kesari, Santosh
AU - Lai, Albert
AU - Lee, Ian Y.
AU - Liau, Linda M.
AU - Mikkelsen, Tom
AU - Nghiemphu, Phioanh Leia
AU - Piccioni, David
AU - Walbert, Tobias
AU - Chu, Alice
AU - Das, Asha
AU - Diago, Oscar R.
AU - Gammon, Dawn
AU - Gruber, Harry E.
AU - Hanna, Michelle
AU - Jolly, Douglas J.
AU - Kasahara, Noriyuki
AU - McCarthy, David
AU - Mitchell, Leah
AU - Ostertag, Derek
AU - Robbins, Joan M.
AU - Rodriguez-Aguirre, Maria
AU - Vogelbaum, Michael A.
N1 - Publisher Copyright:
Copyright 2016 by the American Association for the Advancement of Science; all rights reserved.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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).
AB - 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).
UR - https://www.scopus.com/pages/publications/84973139124
UR - https://www.scopus.com/inward/citedby.url?scp=84973139124&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.aad9784
DO - 10.1126/scitranslmed.aad9784
M3 - Article
C2 - 27252174
AN - SCOPUS:84973139124
SN - 1946-6234
VL - 8
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 341
M1 - 341ra75
ER -
