Article Text

Download PDFPDF

353 Identification of potential response predictors to maveropepimut-S (DPX-Survivac), a novel T cell activating immunotherapy, in patients with advanced recurrent ovarian cancer
  1. Oliver Dorigo1,
  2. Walead Ebrahimizadeh2,
  3. Barry Kennedy2,
  4. Lisa MacDonald2,
  5. Stephan Fiset2,
  6. Jeannine Villella3,
  7. OZA Amit4,
  8. Tanja Pejovic5,
  9. Prafull Ghatage6,
  10. Sharad Ghamande7,
  11. Diane Provencher8 and
  12. Yogesh Bramhecha2
  1. 1Stanford Women’s Cancer Center, Stanford, Standford, CA, USA
  2. 2IMV inc., Dartmouth, Canada
  3. 3Lenox Hill Hospital, New York, NY, USA
  4. 4Princess Margaret Cancer Centre, UHN, Toronto, Canada
  5. 5Oregon Health and Science University, Portland, OR, USA
  6. 6Alberta Health Services, Calgary, Canada
  7. 7Georgia Cancer Center, Augusta, GA, USA
  8. 8Institut du cancer de Montréal, Montreal, Canada


Background Epithelial ovarian cancer (OvCa) is the most lethal of gynecological malignancies. The high mortality is related to a late diagnosis with over 75% being at an advanced stage, high recurrence rates, and ultimately resistance to chemotherapy. Previous studies have consistently demonstrated a strong association between higher tumor T cell infiltration and improved survival in OvCa patients supporting the potential clinical utility of T cell activating immunotherapy approaches. Maveropepimut-S (MVP-S, formerly named DPX-Survivac) is a T cell activating immunotherapy which is a formulation of the proprietary drug delivery platform DPX™ with immunogenic T-cell epitopes derived from the tumor-associated antigen survivin. MVP-S in combination with intermittent low-dose cyclophosphamide has been shown to induce robust and durable antigen-specific T cell responses and anti-tumor clinical activity in recurrent OvCa patients. The current study presents translational data aimed at identifying tumor tissue-based predictive biomarkers for response to treatment with MVP-S.

Methods Baseline and on-treatment tumor biopsies were collected from patients treated with MVP-S primed with immune-modulating low dose cyclophosphamide. Multiplex-immunohistochemistry (mIHC, Akoya Biosciences) and RNAseq analyses (Personalis Inc.) were used to analyze the tumor immune environment and identify potential response predictors to MVP-S.

Results Twenty-two patients with advanced, recurrent OvCa were enrolled in this study. mIHC analysis demonstrated that higher baseline CD3+CD8+ T cell infiltration in tumor tissue was significantly associated with anti-tumor clinical activity of MVP-S defined as >10% on-treatment tumor regression. Pathway enrichment analyses using the differentially expressed genes associated with anti-tumor clinical activity confirmed these findings. In addition, we identified B cell pathway genes to be significantly upregulated in patients with >10% on-treatment tumor regression. mIHC analyses of paired biopsies available for one subject with clinical response (PR) demonstrated that MVP-S treatment induced increased T and B cell infiltration in the on-treatment biopsy compared to the baseline biopsy. These findings suggest that immunogenic tumors are more susceptible to the MVP-S treatment, in line with its mechanism of action. Pathway enrichment analyses further revealed that upregulation of genes or pathways related to immune-suppression (e.g. WNT pathway) or immune evasion/exclusion (CD276, Arg2) were significantly associated with lack of anti-tumor activity indicative of potential mechanism of primary resistance.

Conclusions Collectively, these results provide insight for possible response predictors to MVP-S based therapy

Trial Registration NCT02785250

Ethics Approval The protocol and patient-informed consent form received approval by Institutional Review Boards. Written informed consent was obtained from all patients. REBs: Comite d’ethique de la recherche du CHUM (Montreal, Canada); Western Institutional Review Board 20161075 (Augusta, GA, USA); FWA #00002505 (NEW YORK, NY, USA); FWA00000161, IRB00000471 (Portland, Oregon, USA); University Health Network REB (Toronto, Canada); FWA00000935, FWA00000934 (Standford, CA, USA); Health Research Ethics Board of Alberta, (Edmonton, Canada)

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.