AT-29 INTRAVENOUS ADMINISTRATION OF TOCA 511 IN PATIENTS WITH RECURRENT GLIOBLASTOMA

• Published in: Neuro-oncology (Charlottesville, Va.) Vol. 16; no. suppl 5; p. v15
• Main Authors: Kalkanis, S., Jolly, D. J., Pertschuk, D., Ostertag, D., Robbins, J. M., Huang, T. T., Gruber, H., Mikkelsen, T.
• Format: Journal Article
• Language: English
• Published: 01.11.2014
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/nou237.29

INTRODUCTION: Toca 511 (vocimagene amiretrorepvec) is an investigational retroviral replicating vector (RRV) that encodes the transgene cytosine deaminase (CD). Subsequent oral administration of investigational extended-release 5-FC (Toca FC) results in formation of 5-FU within infected tumor cells expressing CD. A clinical study was initiated to evaluate the delivery of Toca 511 vector to brain tumor via intravenous administration (NCT01985256). METHODS: The primary purpose of this study is to identify the highest safe and well tolerated dose of Toca 511 administered intravenously to subjects with recurrent high grade glioma scheduled for repeat resection. Subjects who have a recurrent high grade glioma who are scheduled for repeat surgical resection will receive an intravenous administration of Toca 511 approximately 11 days prior to surgery. At the time of surgery Toca 511 will be re-administered into the walls of the resection cavity. After 5 weeks, subjects then take oral Toca FC for 7 days every five weeks until study completion or progression. Dose escalation is accelerated for the first three cohorts (single patient cohorts) and the subsequent two cohorts follow a standard 3 + 3 design. Doses are escalated at half-log increases from a total of 4.8x10 proportional to to 4.8x10 arrow right 0 TU. RESULTS: Preclinical studies defined the pharmacokinetics and efficacy of intravenous Toca 511 with intraperitoneal 5-FC in a syngeneic murine brain cancer model. In humans, the first 2 subjects were administered Toca 511 intravenously without complication or toxicity. Peak circulating Toca 511 in the patient in the second dose cohort was present at approximately one billion viral particles per mL of plasma. The half-life of the vector was approximately 5 minutes. Preliminary safety and tolerability data, in addition to pharmacokinetics of Toca 511 in the blood and resected tumor will be reported. CONCLUSION: Toca 511 has been safely administered intravenously and further dose escalation is ongoing.