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

Neuro Oncol. 2015 Jun;17(6):854-61. doi: 10.1093/neuonc/nou348. Epub 2015 Jan 13.


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.

Keywords: ACT III; EGFRvIII; glioblastoma; glioma; rindopepimut.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

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


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