353 Identification of potential response predictors to maveropepimut-S (DPX-Survivac), a novel T cell activating immunotherapy, in patients with advanced recurrent ovarian cancer

Background Epithelial ovarian cancer (OvCa) is the most lethal of gynecological malignancies. The high mortality related to a late diagnosis with over 75% being at an advanced stage, recurrence rates, and ultimately resistance chemotherapy. Previous studies have consistently demonstrated strong association between higher tumor T cell infiltration improved survival in OvCa patients supporting potential clinical utility activating immunotherapy approaches. Maveropepimut-S (MVP-S, formerly named DPX-Survivac) which formulation proprietary drug delivery platform DPX™ immunogenic T-cell epitopes derived from tumor-associated antigen survivin. MVP-S combination intermittent low-dose cyclophosphamide has been shown induce robust durable antigen-specific responses anti-tumor activity recurrent patients. current study presents translational data aimed identifying tissue-based predictive biomarkers for response treatment MVP-S. Methods Baseline on-treatment biopsies were collected treated primed immune-modulating low dose cyclophosphamide. Multiplex-immunohistochemistry (mIHC, Akoya Biosciences) RNAseq analyses (Personalis Inc.) used analyze immune environment identify predictors Results Twenty-two advanced, enrolled this study. mIHC analysis that baseline CD3+CD8+ tissue was significantly associated defined as >10% regression. Pathway enrichment using differentially expressed genes confirmed these findings. In addition, we identified B pathway be upregulated paired available one subject (PR) induced increased biopsy compared biopsy. These findings suggest tumors are more susceptible treatment, line its mechanism action. further revealed upregulation or pathways immune-suppression (e.g. WNT pathway) evasion/exclusion (CD276, Arg2) lack indicative primary resistance. Conclusions Collectively, results provide insight possible based therapy Trial Registration NCT02785250 Ethics Approval protocol patient-informed consent form received approval by Institutional Review Boards. Written informed obtained all REBs: Comite d’ethique de la recherche du CHUM (Montreal, Canada); Western Board 20161075 (Augusta, GA, USA); FWA #00002505 (NEW YORK, NY, FWA00000161, IRB00000471 (Portland, Oregon, University Health Network REB (Toronto, FWA00000935, FWA00000934 (Standford, CA, Research Alberta, (Edmonton, Canada)