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

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

Research output: Contribution to journalArticle

199 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)854-861
Number of pages8
JournalNeuro-oncology
Volume17
Issue number6
DOIs
StatePublished - 2015

Keywords

  • ACT III
  • EGFRvIII
  • Glioblastoma
  • Glioma
  • Rindopepimut

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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    Schuster, J., Lai, R. K., Recht, L. D., Reardon, D. A., Paleologos, N. A., Groves, M. D., Mrugala, M. M., Jensen, R., Baehring, J. M., Sloan, A., Archer, G. E., Bigner, D. D., Cruickshank, S., Green, J. A., Keler, T., Davis, T. A., Heimberger, A. B., & Sampson, J. H. (2015). A phase II, multicenter trial of rindopepimut (CDX-110) in newly diagnosed glioblastoma: The ACT III study. Neuro-oncology, 17(6), 854-861. https://doi.org/10.1093/neuonc/nou348