Phase 1 trial of vocimagene amiretrorepvec and 5-fluorocytosine for recurrent high-grade glioma

Timothy F. Cloughesy, Joseph Landolfi, Daniel J. Hogan, Stephen Bloomfield, Bob Carter, Clark C. Chen, J. Bradley Elder, Steven N. Kalkanis, Santosh Kesari, Albert Lai, Ian Y. Lee, Linda M. Liau, Tom Mikkelsen, Phioanh Leia Nghiemphu, David Piccioni, Tobias Walbert, Alice Chu, Asha Das, Oscar R. Diago, Dawn GammonHarry E. Gruber, Michelle Hanna, Douglas J. Jolly, Noriyuki Kasahara, David McCarthy, Leah Mitchell, Derek Ostertag, Joan M. Robbins, Maria Rodriguez-Aguirre, Michael A. Vogelbaum

Research output: Contribution to journalArticlepeer-review

99 Scopus citations


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).

Original languageEnglish (US)
Article number341ra75
JournalScience Translational Medicine
Issue number341
StatePublished - Jun 1 2016

Bibliographical note

Funding Information:
The authors thank the Accelerate Brain Cancer Cure Foundation (Washington, DC), the National Brain Tumor Society (Watertown, MA), the American Brain Tumor Association (Chicago, IL), the Musella Foundation (Hewlett, NY), and Voices Against Brain Cancer (New York, NY) for their support and collaborations. N.K. was also supported in part by U01NS059821 from the National Institute of Neurological Disorders and Stroke.

Publisher Copyright:
Copyright 2016 by the American Association for the Advancement of Science; all rights reserved.


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