Background: Survivin, a protein involved in regulation of apoptosis, is highly expressed in many tumor types and has reported prognostic value. DPX-Survivac is a cocktail of survivin HLA class I peptides (A1, A2, A3, A24 and B7) formulated in the novel adjuvanting vaccine platform DepoVax. A phase I study examined the safety and immune potency of DPX-Survivac in combination with cyclophosphamide in ovarian cancer patients. Methods: 18 of 19 advanced ovarian cancer patients treated with platinum chemotherapy and showing no disease progression completed their vaccine therapy. Cohort A (6 pts) received three 0.5 mL vaccine injections 3 weeks apart; cohorts B and C (6 pts each) received three 0.1 mL or 0.5 mL vaccine injections in combination with metronomic low dose oral cyclophosphamide. Adverse events were assessed using CTCAE v4.0. Blood was collected to study immune function (MDSCs, T regs and B cells) and vaccine-induced T cell immunity (ELISpot, tetramer analysis and multi-parametric intracellular cytokine staining). Repeated measures of immunity at baseline and after 1, 2 and 3 injections were analyzed using a general linear model. Results: DPX-Survivac was well tolerated with no significant systemic AEs. Local injection AEs occured in all patients. Grade 3 local reactions occured in 3 patients (1 pt in B and 2 pts in C). 11 of 12 patients receiving the combination therapy produced immune responses by at least 2 assays, generally established with one or two vaccinations and increased or maintained with boosters. A dose response was observed, with cohort C patients producing significantly higher magnitude responses (C vs B, P=.013). Low dose cyclophosphamide significantly enhanced the 0.5 ml dose (C vs A, P=.015). Notably, antigen specific CD8 T cells were detected ex vivoi n PBL’s using tetramers and further characterized as polyfunctional by multi-parametric ICS, suggesting a robust immune response. Conclusions: DPX-Survivac is well tolerated and immunogenic. Immune modulation with low dose oral cyclophosphamide can dramatically enhance the immunogenicity of this vaccine. The efficacy of the proposed DPX-Survivac vaccine therapy needs to be tested in a randomized phase II study. Clinical trial information: NCT01416038.