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

Journal Article (Journal Article;Multicenter Study)

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.

Full Text

Duke Authors

Cited Authors

  • Schuster, J; Lai, RK; Recht, LD; Reardon, DA; Paleologos, NA; Groves, MD; Mrugala, MM; Jensen, R; Baehring, JM; Sloan, A; Archer, GE; Bigner, DD; Cruickshank, S; Green, JA; Keler, T; Davis, TA; Heimberger, AB; Sampson, JH

Published Date

  • June 2015

Published In

Volume / Issue

  • 17 / 6

Start / End Page

  • 854 - 861

PubMed ID

  • 25586468

Pubmed Central ID

  • PMC4483122

Electronic International Standard Serial Number (EISSN)

  • 1523-5866

Digital Object Identifier (DOI)

  • 10.1093/neuonc/nou348


  • eng

Conference Location

  • England