REACT: A phase II study of rindopepimut (CDX-110) plus bevacizumab (BV) in relapsed glioblastoma (GB)

TPS2103 Background: EGFRvIII is a constitutively active tumorigenic deletion mutation of EGFR. It is expressed in ~30% of primary GB where it is linked to poor long-term survival (Pelloski 2007). The investigational vaccine rindopepimut consists of the unique EGFRvIII peptide sequence conjugated to keyhole limpet hemocyanin (KLH), delivered intradermally (500ug with 150ug GM-CSF as an adjuvant). Remarkably consistent and promising results across 3 phase II studies in newly diagnosed, resected EGFRvIII+ GB (Lai 2011) represent a statistically significant improvement over a historical control cohort matched for major eligibility criteria (median overall survival [OS] = 24.4 - 24.6 vs. 15.2 months from diagnosis [m] and median progression-free survival [PFS] = 12.3 - 15.3 vs. 6.4 m). ACT IV, a phase III trial in this population, is ongoing. The immunosuppressive influence of residual/advanced GB presents a challenge to activation of efficacious antitumor immune responses. Anecdotal evidence (compassionate use cases, Sampson 2008) suggests that rindopepimut may induce specific immune responses and regression in multifocal and bulky residual tumors. Rindopepimut with BV, which inhibits VEGF and its immunosuppressive properties (including impaired maturation of dendritic cells and disruption of tumoral T cell infiltration [Johnson 2007, Shrimali 2010]) may further optimize EGFRvIII-specific immune response and antitumor activity. Methods: ReACT is a Phase II study of rindopepimut plus BV in patients (pts) with 1st or 2nd relapse of EGFRvIII+ GB. BV-naïve pts will be enrolled to Group 1 (n=70: randomized 1:1 to BV plus either rindopepimut/GM-CSF or control injection [low-dose KLH]) while BV-refractory patients will enter Group 2 (n=25: to receive BV plus open-label rindopepimut/GM-CSF). Concurrent with BV (10 mg/kg, q 2 wks), blinded treatment or open-label vaccine is given in priming phase (days 1, 15 and 29), then monthly until PD. Tumor response is assessed every 8 weeks, and patients are followed for survival after PD. Objectives are PFS at 6 months (primary), objective response rate, PFS, OS, safety, immunogenicity and elimination of EGFRvIII. ReACT opened to accrual in December 2011 (NCT01498328).