Infiltration Of Tumor By T Cells Following Treatment With Dpx-Survivac And Intermittent Low Dose Cyclophosphamide (Cpa) Leads To Clinical Responses In Advanced Recurrent Ovarian Cancer (Ovca).

6075 Background: DPX-Survivac is a novel T-cell activating therapy designed to elicit an effective immune response against survivin expressing tumors. Its unique mechanism of action (MOA) facilitates active and sustained uptake of target peptides by APC at the injection site. APCs subsequently present the antigen in local lymph nodes generating survivin-specific T cells that traffic to distant tumor sites and elicit effective tumor cell death. DPX-Survivac is used in combination with intermittent low dose CPA which acts as an immunomodulator of T-cell responses. Methods: The study enrolled 22 patients with recurrent, advanced platinum-sensitive and -resistant ovarian cancer. Patients received 2 subcutaneous injections of DPX-Survivac 3 weeks apart and every 8 weeks thereafter, and intermittent low dose CPA for up to 1 year. Paired tumor biopsies were performed prior to treatment and on treatment. Primary endpoints were ORR, DCR and safety. Secondary endpoints include cell mediated immunity, immune cell infiltration in paired biopsy samples, DOR, TTP, OS and biomarker analyses. Results: Twenty-two patients were enrolled in the study. Three patients were discontinued prematurely due to early progression leaving 19 patients for response evaluation. The population is heavily pre-treated with a median of 3 lines of prior treatment [range 1 to 8]; 77.3% of patients are platinum-resistant. At the time of data cut-off, 3/19 patients (15.8%) achieved PR and one additional patient met PR on target lesions but had a newly detected lesion; 10/19 patients (52.6%) showed tumor regression on target lesions at > 1 scan. The median time on study (N=19) is 131 days [63 to ˃295]. Six patients are still on trial. The clinical responses and benefits observed with treatment are associated with an increase in systemic survivin-specific T cells and tumor immune-infiltration. Moreover, RNAseq analysis on paired tumor tissue revealed an enrichment in cytolytic T-cell signature. The most common AEs were grade 1-2 injection site reactions; 4 treatment-related SAEs were reported. Conclusions: DPX-Survivac and intermittent low dose CPA shows promising clinical activity in heavily pre-treated patients with recurrent OvCa. The preliminary results, supported by strong translational data, link the observed clinical benefits with the unique MOA of DPX-Survivac. These clinical results suggest that DPX-Survivac/CPA is an active regimen in OvCa and warrant testing in an expanded cohort of patients. Clinical trial information: NCT02785250.