New clinical data from the DeCidE1 trial: Results on DPX-Survivac, low dose cyclophosphamide (CPA), and epacadostat (INCB024360) in subjects with advanced recurrent epithelial ovarian cancer
Authors: O. Dorigo, A.M. Oza, J.L. Tanyi, J. Strauss, T. Pejovic, S. Ghamande, P. Ghatage, J. Villella, S. Fiset, L.D. MacDonald, H. Torrey, G.M. Weir, O. Hrytsenko, M.M. Stanford, R. Newton, L. Leopold, G.N. Rosu
Journal: Annals of Oncology (2018)

Background: DPX-Survivac is a novel T cell activating therapy containing a mix of HLA class I peptides designed to evoke a T cell response against survivin, previously optimized for immunogenicity when delivered with low dose CPA. Epacadostat (E) is a potent, selective IDO-1 inhibitor that may reverse tumour-associated immune suppression. This Phase 1b/2 is evaluating if a de novo tumour-specific T cell response, combined with the alteration of immune suppression will result in clinical benefit. Methods: Ovarian cancer subjects with disease progression were treated with DPX-Survivac (2x 0.25 mL q3w, up to 6x 0.1 mL q8w), low dose CPA (50 mg BID, alternating weeks), and E (up to 300 mg BID). Primary endpoints include safety and immunogenicity. Secondary endpoints include objective response by RECIST 1.1. PBMCs were collected at specific timepoints for immune analysis. Tumour biopsies were collected pre-treatment and at day 56 for analysis of infiltrating immune populations. Results: Enrollment to the Phase 1b is now closed; clinical and immunological analysis is ongoing for treated subjects. Treatments have been well tolerated. Evaluable subjects have shown strong and sustained survivin-specific systemic immune responses by IFN-γ ELISPOT of PBMCs. Survivin-specific T cells cloned from the blood of a subject with tumour regression were also identified in her on-treatment tumour using TCR-β sequencing. Analysis of subpopulations suggests a direct correlation between tumour size and clinical benefit- subjects with sum of target lesion ≤5 cm showing increased tumour regression. Six of 13 subjects with a target lesion sum ≤5 cm showed tumour decrease during treatment. Four partial responses have been observed in this subgroup of subjects and disease control was observed in 9 of 13 subjects. Conclusions: Combination of DPX-Survivac, low dose CPA, and E has demonstrated so far, robust systemic survivin-specific T cell responses and evidence of survivin-specific T cells in the tumour, supporting the mechanism of action of DPX-Survivac. The tumour burden at the time of treatment may correlate with clinical outcome. The combination is well-tolerated. Clinical trial identification: NCT02785250. Legal entity responsible for the study: IMV Inc. Funding: IMV Inc. Incyte Corporation. Disclosure: O. Dorigo: Advisory board: Merck, Geneos, Tesaro; Speaker: AstraZeneca, Tesaro. A.M. Oza: IIT with [IMV Inc.] J. Strauss: Consulting: Tempus; Stock ownership: Abbvie, Abbott Laboratories, Bristol-Myers Squibb, Intuitive Surgical, Johnson & Johnson, Merck. S. Ghamande: Speaker: Tesaro; Consultant: Advaxis, no bearing on this trial. S. Fiset, L.D. MacDonald, G.M. Weir, M.M. Stanford, O. Hrytsenko: Employee of IMV Inc. and own stock in the company. H. Torrey: Employee of IMV Inc. R. Newton, L. Leopold: Employee and shareholder of Incyte corporation. G.N. Rosu: Chief Medical Officer of IMV Inc. and holds stock options for the company. All other authors have declared no conflicts of interest.