Vididencel, an active immunotherapy in high-grade serous ovarian carcinoma patients: Analysis of tumor-directed immune responses post-primary treatment.

5597 Background: Ovarian cancer (OC) remains the most common cause of mortality in gynecologic cancers, with advanced-stage high-grade serous carcinoma (HGSOC) accounting for most cases. PARP inhibitors have provided significant benefits and notable progression-free survival for patients with BRCAmut and HRD+, but survival benefits following primary treatment remains a major clinical challenge. We have conducted a phase 1 trial (NCT04739527) assessing the role of an active immunotherapy, vididencel, in patients with HGSOC post-primary treatment. Vididencel expresses multiple tumor-associated antigens (TAA), including WT1 and PRAME, which are frequently upregulated in HGSOC. Methods: Following primary treatment, patients received 8 doses of vididencel intradermally administered every 14 days, followed by 2 booster injections at week 14 and 18. Peripheral blood mononuclear cells (PBMC) were obtained at week 0, 4, 10, 14, 18 and 22. Disease status was evaluated at week 22 using clinical assessment and CA125 levels. Patients were followed for disease status for 2 years. IFNγ ELISpot was performed on PBMC for WT1, PRAME, MAGEA3/4 and NY-ESO1. Vididencel induced T-cell responses were calculated as ≥2-fold increase of the mock-corrected baseline response. Results: All 17 patients completed treatment phase (up to week 22 or end of treatment). Patient demographics are outlined in table I. 11 out of 17 patients completed predefined 2-year follow-up. With median follow-up of 26.4 months 8 out of 11 patients remain alive. 12 out of 17 patients (71%) showed improved tumor-directed vididencel-induced immune responses (VIR) and are associated with improved progression-free survival. 5 of 12 patients (42%) with VIR still had stable disease, with 2 patients beyond 3.5 years of follow-up. Conclusions: Long-term follow-up of HGSOC patients treated with vididencel confirms safety, tolerability and feasibility resulting in strong T cell response against TAA. The improved tumor-directed responses were associated with better progression-free survival. These data confirm that vididencel is a safe immunotherapy and provides strong basis for novel combination treatments for ovarian cancer patients. Clinical trial information: NCT04739527 . Patient demographics. Demographics Total patients 17 Age(in years) Mean Median Range 61.66443-75 Stage n(%) III IIV 12(70.6) 5(29.4) Primary treatment n(%) PDS IDS 2(11.8)15(88.2) Surgery outcome n(%) Complete Optimal 15(88.2) 2(11.8) CA125 at screening Mean Median Range 21.8207-55 Molecular subtype n(%) BRCAm BRCAwt 13(76.5) 4(23.5) PDS, primary debulking surgery IDS, interval debulking surgery; BRCAm, BRCA mutation; BRCAwt, BRCA wild type.