Autologous heat shock protein vaccine (HSPPC-96) for patients with recurrent glioblastoma (GBM): Results of a phase II multicenter clinical trial with immunological assessments.

Abstract

2565 Background: HSPPC-96 is derived from a patient’s individual tumor and contains glycoprotein-96 (gp96) polypeptide associated with cancer-specific antigenic peptides. Methods: This ongoing single-arm multicenter Phase 2 trial is designed to evaluate overall survival (primary objective) and immunologic response (secondary objective) with HSPPC-96 in patients with first or subsequent recurrence of GBM. Prior treatment with radiotherapy and temozolomide was required. All patients underwent a >90% resection of the recurrence. Vaccine therapy was to be initiated within 5 weeks post-surgery and consisted of 25 µg HSPPC-96, given ID weekly x 4, followed by bi-weekly injections for up to 52 weeks. Results: A total of 33 patients at first recurrence (M:F = 25:8) with a median KPS of 80 were entered. A median of 6 injections (range: 1-15) were administered to the ITT population, with a requisite of 4 vaccinations for the evaluable population. The vaccine was well tolerated with no attributed serious adverse events and no related grade 3 or 4 toxicities. Injection site reaction was seen in 12 patients and fatigue was reported in 9 patients. As of Jan. 2011, the median survival (KM estimates) is 324 days for ITT population (37-877) and 333 days for evaluable population (99-877). 11 patients are still alive and being followed, including 4 beyond one year (374d, 419d, 578d, and 877 days, respectively). All patients with immunological endpoints tested to date exhibited a significant innate immune response and all patients demonstrated CD8 T cell IFN gamma production upon restimulation with autologous gp-96; following vaccine administration. Conclusions: HSPPC-96 evokes a specific and innate immune response in patients with recurrent glioma and survival data available to date indicates HSPPC-96 vaccine provides a possible clinical benefit with a favorable safety profile. Collectively these results provide the impetus for Phase 3 testing against currently approved therapies for patients with recurrent glioblastoma.