Details

Autor(en) / Beteiligte

• Schuster, James
• Lai, Rose K
• Recht, Lawrence D
• Reardon, David A
• Paleologos, Nina A
• Groves, Morris D
• Mrugala, Maciej M
• Jensen, Randy
• Baehring, Joachim M
• Sloan, Andrew
• Archer, Gary E
• Bigner, Darell D
• Cruickshank, Scott
• Green, Jennifer A
• Keler, Tibor
• Davis, Thomas A
• Heimberger, Amy B
• Sampson, John H

Titel

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

Ist Teil von

• Neuro-oncology (Charlottesville, Va.), 2015-06, Vol.17 (6), p.854-861

Ort / Verlag

England: Oxford University Press

Erscheinungsjahr

2015

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

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