IT-09PHASE I STUDY OF SAFETY, TOLERABILITY AND IMMUNOLOGIC EFFECTS OF A SURVIVIN PEPTIDE MIMIC VACCINE (SurVaxM) IN PATIENTS WITH RECURRENT MALIGNANT GLIOMA

BACKGROUND: Survivin is an inhibitor of apoptosis protein (IAP) that is highly expressed in malignant gliomas and other cancers. Induction of cytotoxic immunity against survivin is an attractive antitumor strategy. Preclinical studies demonstrated the ability of a KLH-conjugated survivin peptide mimic (SVN53-67/M57-KLH; SurVaxM) to induce an immune response capable of inhibiting the growth of gliomas in mice, and killing human glioma cells ex vivo. The vaccine is predicted to be immunogenic in humans with HLA-A*02, HLA-A*03, HLA-A*24 and other haplotypes and pre-clinical studies demonstrate potent and specific cytokine-supported antitumor CTL responses. METHODS: Nine patients with survivin-positive, recurrent malignant gliomas and either HLA-A*02 or HLA-A*03 haplotypes received a series of 4 subcutaneous injections of SurVaxM at 2 week intervals. MRIs were performed at baseline, week 8, and at subsequent intervals. RESULTS: SurVaxM was well tolerated with no SAE, and mostly grade one AE. 6 of 9 patients experienced grade 1 localized erythema at the injection site, likely related to the vaccine. 3 patients reported grades 1 or 2 fatigue, 2/9 experienced myalgia, possibly related to the study drug. Grade 1 lymphopenia was seen in 3/9 patients and grade 1 or 2 leukopenia was recorded in 3 patients. The only grade 3 AE, a seizure, was not related to the vaccine. The majority of patients developed specific cellular and humoral immune responses to survivin and 3 of 8 patients (all with GBM), who are evaluable for clinical response, have stable disease after more than 12 months of follow-up. All others have had progressive disease. Survival data will be described. CONCLUSION: This study demonstrated the safety and tolerability of SurVaxM in patients with recurrent or progressive malignant glioma following failure of standard therapy. SurVaxM proved to be immunogenic in most patients. A phase II clinical trial of SurVaxM is planned.