A phase I/II study of the safety and efficacy of intraperitoneal IMNN-001 in combination with neoadjuvant chemotherapy (NACT) of paclitaxel and carboplatin in patients newly diagnosed with advanced epithelial ovarian cancer (EOC): Updated survival an

5516 Background: OVATION-2 (NCT03393884) is a randomized, controlled phase I/II study evaluating IMNN-001 in newly diagnosed advanced epithelial ovarian cancer (EOC) patients. The study’s purpose was to assess safety and efficacy of IMNN-001, an interleukin-12 (IL-12) gene therapy in combination with standard of care (SoC) chemotherapy. Methods: Patients were randomized 1:1 to NACT alone or NACT +IMNN-001. Carboplatin/paclitaxel IV was administered every 21 days for 3 cycles before and after interval debulking surgery (IDS) in the control arm, and concurrently with intraperitoneal IMNN-001 given weekly for 8 weeks prior to and for 9 weeks after IDS in the experimental arm. PFS was the primary endpoint with secondaries of OS, chemotherapy response score (CRS), surgical response score (SRS) and overall response rate (ORR). Hazard ratios are reported for PFS and OS as the study was not powered for statistical significance. Additional statistical methods quantified Totality of Evidence (ToE, Wang et al 2023, Claggett 2022) by considering PFS and OS outcomes simultaneously. Data lock was June 2024, with OS updated with data through November 2024. Results: 112 patients were enrolled with a median follow-up 31 months. Stage IV disease (31.0% vs 22.2%) and ECOG PS≥1 (48.3% vs 35.2%) were more common in the experimental arm. PARPi maintenance was less frequent in the experimental arm (32.8% vs 44.4%) despite balanced HRD status. IMNN-001 was well-tolerated with common adverse events (AEs) primarily including abdominal pain, nausea, and vomiting. There was no report of cytokine release syndrome or elevated risk of immune-related adverse events. Median PFS was 14.9 vs 11.9 months (HR:0.79, 95% CI: 0.51-1.23), and median OS was 46.0 vs 33.0 months (HR:0.69, 95% CI: 0.4-1.19) favoring the experimental arm. Rates of CRS with CRS3 outcome (complete or near complete response) and SRS R0 Section outcome were higher in the experimental arm; ORR was similar. In investigator choice PARPi subgroups, median PFS was 33.8 vs 22.1 months favoring the experimental arm (HR:0.79, 95% CI: 0.51-1.23), median OS was not reached in the experimental arm vs 37.1 months in the control arm (HR:0.38, 95% CI: 0.13-1.06). By simultaneously considering individual patients' progression and death times (ToE), the experimental arm shows 6.5 months improvement (less time lost) compared to the control arm with one-sided p = 0.375. Conclusions: IMNN-001 demonstrated trends towards material improvement in overall survival and acceptable safety in advanced EOC, especially in HRD+ patients. These results are supportive of further development in the upcoming pivotal phase 3 study. Clinical trial information: NCT03393884 .