Survaxm With Standard Therapy In Newly Diagnosed Glioblastoma: Phase Ii Trial Update.

2016 Background: SVN53-67/M57-KLH (SurVaxM) is a novel cancer vaccine designed to stimulate an immune response targeting the tumor-specific antigen survivin. A multi-center, single-arm phase 2 clinical trial of SurVaxM in survivin-positive newly diagnosed glioblastoma (nGBM, NCT02455557) is now fully enrolled and data updated. Methods: Patients (n = 63) with nGBM were enrolled at 5 US cancer centers and followed for safety, 6-month progression-free survival (PFS6), 12-month overall survival (OS12) and immunologic response. All patients underwent craniotomy with near-total resection ( < 1 cm 3 residual contrast enhancement), TMZ chemoradiation, adjuvant TMZ and SurVaxM. Patients received 4 doses of SurVaxM (500 mcg) in Montanide with sargramostim (100 mcg) biweekly, followed by maintenance SurVaxM with adjuvants every 12 weeks until tumor progression. Immunogenicity of SurVaxM was assessed by detection of survivin-specific antibody (IgG) and CD8+ T-cell levels. Results: Median age was 60 yrs (range, 20-82), 53% methylated MGMT, 46% unmethylated MGMT (1 N/A) and 60% were male. Survivin expression ranged from 1-40% (median 12%) by immunohistochemistry. Median time to first immunization was 3.0 mo (1.9-4.0 mo) from diagnosis. There have been no RLT or grade ≥ 3 SAE attributable to SurVaxM. The most common AE was grade 1-2 injection site reactions. OS12 was 86% from first immunization and 93.4% from diagnosis. OS12 for meMGMT was 93.1% and unMGMT was 78% from first immunization. Median time to tumor progression (mPFS) was 13.9 months from diagnosis. Median OS has not yet been reached. SurVaxM produced an increase in survivin-specific IgG titre from pre-vaccine baseline to ≥ 1:10,000 in 67% of pts and ≥ 1:100,000 in 27%. CD8+ T cell responses were observed. Anti-survivin IgG and OS were correlated. Conclusions: SurVaxM immunotherapy generated encouraging efficacy and immunogenicity in nGBM and has minimal toxicity. A randomized, prospective trial of SurVaxM in nGBM is planned. Clinical trial information: NCT024455557.