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

@entity1 @entity470 @entity5 @entity2903 @entity463
BACKGROUND: The @entity470 variant III deletion mutation, EGFRvIII, is expressed in    30% of @entity463 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 @entity2903 chemotherapy were administered to 65 @entity1 with newly diagnosed EGFRvIII-expressing (EGFRvIII+) @entity463 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 @entity1 , and increased with duration of treatment. EGFRvIII was eliminated in 4/6 (67%) @entity5 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.
