IMNN-001 Plus Neoadjuvant Chemo Improves OS in Advanced Ovarian Cancer

IMNN-001, a DNA-based immunotherapy, combined with neoadjuvant and adjuvant chemotherapy improved overall survival (OS) compared with chemotherapy alone for patients with newly diagnosed advanced ovarian cancer, according to updated results from the phase 2 OVATION 2 trial (NCT03393884), which were announced in a press release from the developer, IMUNON.¹

The most recent data announcement revealed that the median OS was 45.1 months with the IMNN-001 and chemotherapy combination vs 30.4 months with chemotherapy alone; a 14.7-month difference. Furthermore, among patients treated with IMNN-001 and chemotherapy plus PARP inhibitors as part of maintenance therapy, the median OS was 65.6 months vs 41.4 months in the chemotherapy alone group; a 24.2-month increase.

Investigators highlighted that in previously reported data from the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, the median OS was 40.5 months in the IMNN-001 group vs 29.4 months in the chemotherapy alone group, noting that there has been an increase in survival since.² Additionally, in September 2025, It was reported that the IMNN-001 combination produced key anticancer immune cytokines following treatment.³

“It is very encouraging to see results from the OVATION 2 trial indicating that treatment with IMNN-001 was associated with an [OS] benefit of more than a year in patients treated with IMNN-001 plus chemotherapy and more than 2 years in women also receiving PARP inhibitors as part of maintenance therapy. These new findings are especially exciting given that there have been no meaningful advances in standard of care in ovarian cancer in the last 30 years,” stated Premal H. Thaker, MD, the chief of Gynecologic Oncology, David & Lynn Mutch Distinguished Professor of Obstetrics and Gynecology, and director of Gynecologic Oncology Clinical Research at Washington University School of Medicine, and study chair of the OVATION 2 trial and the phase 3 OVATION 3 trial (NCT06915025).¹ “Importantly, with these new efficacy results, IMNN-001 continues to maintain a highly favorable safety and tolerability profile, further reinforcing the potential of this IL-12 immunotherapy to represent a landmark advance in treatment for women who are in desperate need of new and improved treatment options.”

OVATION 2 Trial Breakdown and Design

The OVATION 2 trial evaluated the safety, dosing, efficacy, and biological activity of intraperitoneal IMNN-001 plus chemotherapy vs chemotherapy alone in patients with newly diagnosed advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer. A total of 112 patients were randomly assigned 1:1 to either standard chemotherapy in combination with IMNN-001 or chemotherapy alone. IMNN-001 was administered at 100 mg/m² for up to 17 weekly doses. Following standard-of-care neoadjuvant/adjuvant chemotherapy, patients underwent interval debulking surgery followed by 3 additional cycles of adjuvant chemotherapy to treat any residual tumor.

Eligible patients in the trial had suspected histologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with FIGO stage III or IV disease and specified histologic epithelial cell types, including high grade serous adenocarcinoma, among others.⁴ Patients also had adequate bone marrow, renal, hepatic, and neurologic function, as well as an ECOG performance status from 0 to 2.

Safety and Tolerability Observations

Previous safety data showed that any-grade treatment-emergent adverse effects (TEAEs) occurred in 100% of the IMNN-001 arm and 96.6% of the chemotherapy alone arm.² Serious TEAEs occurred in 72.9% and 36.2% of patients, with TEAEs of special interest in 66.1% and 27.6%.

Furthermore, TEAEs led to dose reduction of IMNN-001 in 15.2%, and 1 patient died in the IMNN-001 cohort due to pancytopenia and respiratory failure.

Reference

1. IMUNON reports updated Phase 2 data showing continued strengthening of overall survival in the OVATION 2 study of IMNN-001 in advanced ovarian cancer. News release. IMUNON. March 25, 2026. Accessed March 25, 2026. https://tinyurl.com/4njef748
2. Thaker P, Richardson D, Hagemann A, et al. 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 analysis from OVATION-2 trial. J Clin Oncol. 2025;43(suppl 16):5516. doi:10.1200/JCO.2025.43.16_suppl.5516
3. IMUNON presents IMNN-001 phase 2 translational data in advanced ovarian cancer demonstrating 13-month OS extension via tumor micro-environment shift. News release. IMUNON. September 22, 2025. Accessed March 25, 2026. https://tinyurl.com/3swkmedy
4. Study of IMNN-001 (also known as GEN-1) with NACT for treatment of ovarian cancer (OVATION 2) (OVATION 2). ClinicalTrials.gov. Updated February 27, 2026. Accessed March 25, 2026. https://tinyurl.com/mr3np8kh