IT-02 * INITIATION OF CLINICAL STUDIES WITH SL-701, A SYNTHETIC MULTI-PEPTIDE VACCINE WITH ENHANCED IMMUNOSTIMULATORY PROPERTIES TARGETING MULTIPLE GLIOMA-ASSOCIATED ANTIGENS, IN ADULTS WITH FIRST RECURRENCE OF GLIOBLASTOMA

Immune targeting presents an important therapeutic approach in glioblastoma (GBM). The SL-701 vaccine, a synthetic multi-peptide designed to induce maximal activation of the immune system against key targets in gliomas involving adults and children, demonstrated tumor regression and durable complete and partial responses when administered in combination with poly:ICLC in investigator-sponsored Phase 1/2 trials in adults with GBM and children with high- grade glioma and diffuse intrinsic pontine glioma (Okada et al., JCO, 29(3):330-6 2011; Pollack et al., JCO 2014 in press). We present an optimized version of this therapy for enhanced immune stimulation with the addition of a synthetic, highly immunogenic mutant to target survivin, a member of the inhibitor of apoptosis family of proteins that is overexpressed in tumors. Other immunogenic mutant peptides in SL-701 target interleukin-13 receptor alpha-2 (IL-13Rα2), which has also been constructed with an amino acid substitution to enhance immunostimulatory activity, and ephrin A2 (EphA2). Most glioma cell lines and primary tumor tissues from patients studied to date express 2 or 3 of these targets. Additionally, target expression was seen on cancer stem cells (CSCs) of GBM. Along with SL-701's well-selected peptide constituents, the immunostimulants GM-CSF and imiquimod, which activate multiple arms of the immune system, will be co-administered to further augment the immune response. Treatment will be delivered as a subcutaneous injection every 2 weeks for 6 months and every 28 days thereafter. This optimized version of SL-701 is now entering a multicenter clinical trial for adult patients with first recurrence GBM with the primary endpoints of overall response rate and overall survival.