Phase I Study Of Survaxm In Patients With Survivin-Expressing Recurrent Malignant Gliomas

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PABackground: Recent studies using SurVaxM, a survivin based multi-epitope cryptic peptide mimic, show specific CD8+ T cell responses and specific CD4+ T cell stimulation. Currently SurVaxM has completed a phase I clinical trial designed to study its safety, tolerability and immunological effects in patients with survivin-positive recurrent malignant gliomas.Survivin is an intracellular inhibitor of apoptosis protein (IAP) that mediates a number of anti-apoptotic and oncogenic effects and is highly expressed in malignant gliomas and other cancers. The vaccine is 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 related to vaccine administration. Most AE were grade 1, including 6 of 9 patients with grade 1 localized erythema at the injection site. Three 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 recurrent glioblastoma), who are evaluable for clinical response, had stable disease after 17-26 months of ongoing follow-up. Five others have had progressive disease, although 4 of these maintained stable disease for 8-14 months.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. By activating multiple CD8+ CTL responses and CD4+ helper support, SurVaxM has a significant theoretical advantage as an active specific immunogen compared with survivin vaccines using a single class I-restricted peptide, or ones that incorporate generic helper peptides, which produce non-specific helper support. Early indicators point to a strong rationale for continued study. A phase II clinical trial of SurVaxM is planned.Citation Format: Michael J. Ciesielski, Laszlo Mechtler, Kathleen Mogensen, Jingxin Qiu, Manmeet Ahluwalia, Kelvin Lee, Alex Adjei, Robert Fenstermaker. Phase I study of SurVaxM in patients with survivin-expressing recurrent malignant gliomas. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT301. doi:10.1158/1538-7445.AM2015-CT301