Phase I/II study of Safety and Efficacy of Intraperitoneal IMNN-001 with Neoadjuvant Chemotherapy of Paclitaxel and Carboplatin in Patients Newly Diagnosed with Advanced Epithelial Ovarian Cancer
Publication Title
SITC Annual Meeting; November 6-10; Houston, TX.2024: 1505
Document Type
Abstract
Publication Date
11-1-2024
Keywords
oregon; chiles
Abstract
OVATION-2 (NCT03393884) is a randomized, open label study assessing IMNN-001, a formulated interleukin-12 DNA plasmid with a synthetic carrier, in addition to neoadjuvant chemotherapy (NACT) for the treatment of newly diagnosed advanced epithelial ovarian cancer (EOC). Methods:Patients received 3 cycles of NACT followed by interval debulking surgery, and 3 additional chemotherapy cycles in both arms. In the experimental arm, IMNN-001 was administrered intraperitoneally weekly concurrently to chemotherapy. The primary endpoint was progression-free survival (PFS). Overall survival (OS), Chemotherapy-Response-Score (CRS), Surgical-Response-Score (SRS) and Objective-Response-Rate (ORR) were secondary endpoints. Although the study was not powered for hypothesis testing, PFS and OS were summarized using the estimate of the harzard ratio and corresponding condfidence interval. Percent response is reported for other endpoints. Results:112 (ITT population) were enrolled with a median follow-up of 24 months at data cutoff (06/21/2024). Patient characteristics were balanced except for an increased proportion of stage IV disease, and lesser proportion of ECOG PS=0 in the experimental arm (31.0% vs 22.2% and 51.7% vs 64.8%, respectively). Patients also received PARP inhibitor maintenance more frequently in the control vs experimental arm (44.4% vs 32.8%). Patients with a pathogenic BRCA mutation and/or HRD status were balanced across the control and experimental arms, 29.6% vs 33.3% respectively. IMNN-001 was well-tolerated with common adverse events primarily gastrointestinal (abdominal pain, nausea, vomiting). Cytokine release syndrome did not occur. Median PFS was 14.9 m for experimental arm vs 11.9 m for control with HR:0.79 (0.51, 1.23). Median OS was 40.5 for experimental arm vs 29.4 m for control with HR:0.74 (0.42, 1.30). Surrogate endpoints of SRS and CRS show a higher response rate in the experimental vs control arm (RO SRS: 64.6% vs 52.1%; CRS 3: 26.1% vs 13.0% respectively). ORR complete response rates were comparable across treatment arms (1.9% control vs 1.7% experimental). In a subgroup analysis of patients having received a PARP inhibitor during the treatment (n=31 PARPi first line, n=43 PARPi any line), median PFS for experimental arm was 33.8m vs 22.1 m for control with HR:0.80 (0.31, 2. 12) and median OS was not reached for experimental arm vs 37.1 m for control with HR:041 (0.13, 1.28) Conclusions: IMNN-001 shows a promising benefit on survival and an acceptable safety profile in patients with newly diagnosed advanced EOC. Results across endpoints show a consistent treatment effect. A Phase 3 study is being designed to confirm these preliminary findings.
Area of Special Interest
Cancer
Area of Special Interest
Women & Children
Specialty/Research Institute
Oncology
Comments
Premal TH, Richardson DL, Hagemann A, Holloway R, Reed M, Bergman M, Pothuri B, DePasquale S, Scalici J, Bregar A, Darus C, Finkelstein K, Leath C, Bell M, Warshal D, Agajanian R, Indermaur M, Mendivil A, Provencher D, Borys N, Hazard S, Musso L, Lindborg S, Anwer K, Bradley W