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

作者：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.^*

来源：Neuro-Oncology, 2015, 17(6): 854-861.

DOI：10.1093/neuonc/nou348

• ACT III
• EGFRvIII
• glioblastoma
• glioma
• rindopepimut

Background. The epidermal growth factor receptor variant III deletion mutation, EGFRvIII, is expressed in similar to 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 (similar to 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.

• 出版日期2015-6