A phase II, multicenter trial of rindopepimut (CDX-110) in newly diagnosed glioblastoma: the ACT III study.

Abstract

BACKGROUND:

The epidermal growth factor receptor variant III deletion mutation, EGFRvIII, is expressed in ∼30% of primary glioblastoma and linked to poor long-term survival. Rindopepimut consists of the unique EGFRvIII peptide sequence conjugated to keyhole limpet hemocyanin. In previous phase II trials (ACTIVATE/ACT II), rindopepimut was well tolerated with robust EGFRvIII-specific immune responses and promising progression-free and overall survival. This multicenter, single-arm phase II clinical trial (ACT III) was performed to confirm these results.

METHODS:

Rindopepimut and standard adjuvant temozolomide chemotherapy were administered to 65 patients with newly diagnosed EGFRvIII-expressing (EGFRvIII+) glioblastoma after gross total resection and chemoradiation.

RESULTS:

Progression-free survival at 5.5 months (∼8.5 mo from diagnosis) was 66%. Relative to study entry, median overall survival was 21.8 months, and 36-month overall survival was 26%. Extended rindopepimut vaccination (up to 3.5+ years) was well tolerated. Grades 1-2 injection site reactions were frequent. Anti-EGFRvIII antibody titers increased ≥4-fold in 85% of patients, and increased with duration of treatment. EGFRvIII was eliminated in 4/6 (67%) tumor samples obtained after >3 months of therapy.

CONCLUSIONS:

This study confirms, in a multicenter setting, the preliminary results seen in previous phase II trials of rindopepimut. A pivotal, double-blind, randomized, phase III trial ("ACT IV") is under way.

• Authors: James Schuster, Rose K Lai, Lawrence D Recht, David A Reardon, Nina A Paleologos, Morris D Groves, Maciej M Mrugala, Randy Jensen, Joachim M Baehring, Andrew Sloan, Gary E Archer, Darell D Bigner, Scott Cruickshank, Jennifer A Green, Tibor Keler, Thomas A Davis, Amy B Heimberger, John H Sampson
• Journal: Neuro-oncology (Neuro Oncol) Vol. 17 Issue 6 Pg. 854-61 (Jun 2015) ISSN: 1523-5866 [Electronic] England
• PMID: 25586468 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Antineoplastic Agents
• Cancer Vaccines
• Vaccines, Subunit
• epidermal growth factor receptor VIII
• Dacarbazine
• ErbB Receptors
• rindopepimut
• Temozolomide

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (therapeutic use)
• Brain Neoplasms (drug therapy, mortality, radiotherapy)
• Cancer Vaccines (therapeutic use)
• Chemoradiotherapy, Adjuvant
• Dacarbazine (analogs & derivatives, therapeutic use)
• Disease-Free Survival
• ErbB Receptors (genetics)
• Female
• Glioblastoma (drug therapy, mortality, radiotherapy)
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Temozolomide
• Treatment Outcome
• Vaccines, Subunit (therapeutic use)