Addition of EGFR-Targeting Vaccine to Temozolomide in EGFRvIII-Expressing Glioblastoma


Key Points

  • In newly diagnosed EGFRvIII-positive glioblastoma, the addition of rindopepimut to temozolomide did not improve survival in patients with minimal residual disease.
  • No difference in survival was seen between the rindopepimut and control groups in the intent-to-treat population.

The phase III ACT IV study has shown no survival benefit of adding rindopepimut, a vaccine targeting the epidermal growth factor receptor (EGFR) deletion mutation EGFRvIII, to temozolomide in patients with newly diagnosed EGFRvIII-positive glioblastoma. These findings were reported by Weller et al in The Lancet Oncology.

Study Details

In the double-blind trial, 745 patients from 165 sites in 22 countries who had undergone maximal surgical resection and completed standard chemoradiation therapy without disease progression were randomized between April 2012 and December 2014 to receive rindopepimut and temozolomide (n = 371) or control vaccine and temozolomide (n = 374). Among the 745 patients, 405 had minimal residual disease, including 195 in the rindopepimut group and 210 in the control group, and 338 had significant residual disease.

Treatment consisted of rindopepimut at 500 μg mixed with 150 μg of granulocyte macrophage colony-stimulating factor or control vaccine (100 μg keyhole limpet hemocyanin) via monthly intradermal injection until disease progression or intolerance and standard oral temozolomide at 150 to 200 mg/m² for 5 of 28 days for 6 to 12 cycles or longer. The primary endpoint was overall survival in patients with minimal residual disease.

No Survival Difference

The study was terminated for futility after a preplanned interim analysis. At final analysis, median overall survival among patients with minimal residual disease was 20.1 months in the rindopepimut group vs 20.0 months in the control group (hazard ratio [HR] = 1.01, P = .93). Among all patients in the intent-to-treat population, median overall survival was 17.4 months vs 17.4 months (HR = 0.89, P = .22).


The most common grade 3 or 4 adverse events in the full rindopepimut group were thrombocytopenia (9% vs 6% in control group), fatigue (2% vs 5%), brain edema (2% vs 3%), seizure (2% vs2%), and headache (2% vs 3%). Serious adverse events included seizure (5% vs 6%) and brain edema (2% vs 3%). One death, due to pulmonary embolism, was considered potentially related to rindopepimut.

The investigators concluded: “Rindopepimut did not increase survival in patients with newly diagnosed glioblastoma. Combination approaches potentially including rindopepimut might be required to show efficacy of immunotherapy in glioblastoma.”

The study was funded by Celldex Therapeutics, Inc.

Michael Weller, MD, of the University Hospital Zurich, is the corresponding author of The Lancet Oncology article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.