87P - New clinical data from the DeCidE1 trial: Results on DPX-Survivac, low dose cyclophosphamide (CPA), and epacadostat (INCB024360) in subjects with a...

Date 14 December 2018
Event ESMO Immuno-Oncology Congress 2018
Session Poster Display session
Presenter Oliver Dorigo
Citation Annals of Oncology (2018) 29 (suppl_10): x24-x38. 10.1093/annonc/mdy487
Authors O. Dorigo1, A.M. Oza2, J.L. Tanyi3, J. Strauss4, T. Pejovic5, S. Ghamande6, P. Ghatage7, J. Villella8, S. Fiset9, L.D. MacDonald9, H. Torrey9, G.M. Weir9, O. Hrytsenko9, M.M. Stanford9, R. Newton10, L. Leopold11, G.N. Rosu9
  • 1Department Of Obstetrics And Gynecology, Stanford University, 94305 - Palo Alto/US
  • 2Medical Oncology And Hematology, Princess Margaret Cancer Center, M5G 2M9 - Toronto/CA
  • 3Division Of Gynecologic Oncology, University of Pennsylvania, Philadelphia/US
  • 4Oncology, Mary Crowley Cancer Research Center, Dallas/US
  • 5Division Of Gynecologic Oncology, Oregon Health and Science University, Portland/US
  • 6Department Of Obstetrics And Gynecology, Augusta University, Augusta/US
  • 7Clinical Trials Unit, Tom Baker Cancer Center, Calgary/CA
  • 8Gynecologic Oncology, Lenox Hill Hospital, New York/US
  • 9Clinical Research, IMV Inc., B3B 2C4 - Dartmouth/CA
  • 10Translational Sciences, Incyte Corporation, Wilmington/US
  • 11Clinical Development, Incyte Corporation, Wilmington/US

Abstract

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.

Editorial acknowledgement

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.