Durable complete responses in some recurrent highgrade glioma patients treated with Toca 511+Toca FC

被引：134

作者：

Cloughesy, Timothy F. ^{[1
,2
]}

Landolfi, Joseph ^{[3
]}

Vogelbaum, Michael A. ^{[4
]}

Ostertag, Derek ^{[5
]}

Elder, James B. ^{[7
]}

Bloomfield, Stephen ^{[3
]}

Carter, Bob ^{[6
]}

Chen, Clark C. ^{[6
]}

Kalkanis, Steven N. ^{[8
]}

Kesari, Santosh ^{[6
]}

Lai, Albert ^{[1
,2
]}

Lee, Ian Y. ^{[8
]}

Liau, Linda M. ^{[1
,2
]}

Mikkelsen, Tom ^{[8
]}

Nghiemphu, Phioanh ^{[1
,2
]}

Piccioni, David ^{[6
]}

Accomando, William ^{[5
]}

Diago, Oscar R. ^{[5
]}

Hogan, Daniel J. ^{[5
]}

Gammon, Dawn ^{[5
]}

Kasahara, Noriyuki ^{[5
,9
,10
]}

Kheoh, Thian ^{[5
]}

Jolly, Douglas J. ^{[5
]}

Gruber, Harry E. ^{[5
]}

Das, Asha ^{[5
]}

Walbert, Tobias ^{[8
]}

机构：

[1] Univ Calif Los Angeles, Dept Neurooncol, Los Angeles, CA USA

[2] Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA USA

[3] JFK Brain Tumor Ctr, New Jersey Neurosci Inst, Edison, NJ USA

[4] Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA

[5] Tocagen Inc, San Diego, CA USA

[6] Univ Calif San Diego, Moores Canc Ctr, Dept Neurosci, San Diego, CA 92103 USA

[7] Ohio State Univ, Wexner Med Ctr, Columbus, OH 43210 USA

[8] Henry Ford Hosp, Detroit, MI 48202 USA

[9] Univ Miami, Dept Cell Biol, Coral Gables, FL 33124 USA

[10] Univ Miami, Dept Pathol, Coral Gables, FL 33124 USA

来源：

NEURO-ONCOLOGY | 2018年 / 20卷 / 10期

关键词：

durable response rate; gene therapy; immuno-oncology; immunotherapy; recurrent high grade glioma; RETROVIRAL REPLICATING VECTOR; 511; GENE-TRANSFER; GLIOBLASTOMA-MULTIFORME; MISMATCH REPAIR; CLINICAL-TRIALS; PHASE-II; TEMOZOLOMIDE; 5-FLUOROCYTOSINE; CRITERIA; BRAIN;

D O I：

10.1093/neuonc/noy075

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Background. Vocimagene amiretrorepvec (Toca 511) is an investigational gamma-retroviral replicating vector encoding cytosine deaminase that, when used in combination with extended-release 5-fluorocytosine (Toca FC), results preclinically in local production of 5-fluorouracil, depletion of immune-suppressive myeloid cells, and subsequent induction of antitumor immunity. Recurrent high-grade glioma (rHGG) patients have a high unmet need for effective therapies that produce durable responses lasting more than 6 months. In this setting, relapse is nearly universal and most responses are transient. Methods. In this Toca 511 ascending-dose phase I trial (NCT01470794), HGG patients who recurred after standard of care underwent surgical resection and received Toca 511 injected into the resection cavity wall, followed by orally administered cycles of Toca FC. Results. Among 56 patients, durable complete responses were observed. A subgroup was identified based on Toca 511 dose and entry requirements for the follow-up phase III study. In this subgroup, which included both isocitrate dehydrogenase 1 (IDH1) mutant and wild-type tumors, the durable response rate is 21.7%. Median duration of follow-up for responders is 35.7+ months. As of August 25, 2017, all responders remain in response and are alive 33.9+ to 52.2+ months after Toca 511 administration, suggesting a positive association of durable response with overall survival. Conclusions. Multiyear durable responses have been observed in rHGG patients treated with Toca 511 + Toca FC in a phase I trial, and the treatment will be further evaluated in a randomized phase III trial. Among IDH1 mutant patients treated at first recurrence, there may be an enrichment of complete responders.

引用

页码：1383 / 1392

页数：10

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