IMNN-001 Continues to Show Favorable Responses in Ovarian Cancer

IMNN-001 demonstrated positive shifts in the tumor microenvironment (TME) along with a favorable safety profile when used for the treatment of newly diagnosed advanced ovarian cancer, according to recent translational data from the phase 2 OVATION-2 study (NCT03393884).¹

When combined with standard-of-care neoadjuvant and adjuvant chemotherapy, IMNN-001, a gene-based interleukin-12 (IL-12) immunotherapy, yielded positive changes in the local TME to favorable immune stimulatory T cell ratios and a TME shift in favor of decreased immunosuppression cells and increased immunostimulatory cells. Additionally, IMNN-001 appears to create a “hot” anti-TME by increasing recruitment of antitumor CD8-positive cells and myeloid dendritic cells.

“These new translational data are very encouraging and strongly reinforce and are consistent with the unprecedented positive overall survival results previously reported from the OVATION-2 Study,” said Douglas V. Faller, MD, PhD, chief medical officer of IMUNON, in a press release.¹ “Results from the study continue to validate our TheraPlas® technology and the broad impact of IMNN-001 on important cancer-fighting cytokines, effectively turning the tumor microenvironment from ‘cold’ to ‘hot’ by activating both innate and adaptive immune systems, with limited to no systemic toxicities.”

Data from OVATION-2 were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and showed that, at a median follow-up of 24 months, IMNN-001 plus chemotherapy led to a median progression-free survival of 14.9 months (95% CI, 12.55–21.19) vs 11.9 months (95% CI, 10.09–14.92) with chemotherapy alone (HR, 0.79; 95% CI, 0.51–1.23).²

At 24 months, the median overall survival (OS) was 40.5 months (95% CI, 28.09–not evaluable [NE]) in the IMNN-001 cohort vs 29.4 months (95% CI, 24.94–45.60) in the chemotherapy cohort (HR, 0.74; 95% CI, 0.42–1.30; P =.2963). With follow-up extended to 31 months, the median OS was 46.0 months (95% CI, 39.20–NE) and 33.0 months (95% CI, 27.14–NE), respectively (HR, 0.69; 95% CI, 0.40-1.19; P =.1865).

“IMNN-001 has shown significant therapeutic potential in clinical trials thus far, and the robust survival benefits and favorable safety profile observed align with these translational findings, supporting our ongoing phase 3 OVATION-3 trial [NCT06915025]. We look forward to advancing the phase 3 trial as quickly as possible for the many women with advanced ovarian cancer who are in urgent need of new, innovative treatment options,” Faller added in the press release.¹

In March 2025, the FDA aligned with IMUNON, the sponsor, on the protocol for the OVATION-3 trial.³ In July 2025, IMUNON announced that the first patient was dosed in the OVATION-3 study.⁴

OVATION-3 is assessing the safety and efficacy, with a primary end point of OS, of IMNN-001 plus neoadjuvant and adjuvant chemotherapy of paclitaxel and carboplatin vs standard-of-care chemotherapy in patients with newly diagnosed stage 3C or 4 ovarian cancer. There is also a subgroup population of patients with homologous recombination deficiency (HRD), including BRCA1 or BRCA2 mutations. Patients who are HRD-positive will also receive a PARP inhibitor as part of standard maintenance therapy.

FAQs

What is IMNN-001?

IMNN-001 is an investigational immunotherapy that uses a novel approach to stimulate a patient's own immune system to fight cancer. It can be defined by three key characteristics. It is a DNA-mediated, IL-12 gene immunotherapy. This means it delivers the genetic code for interleukin-12 (IL-12), a powerful, naturally occurring protein that activates immune cells. It is built on IMUNON, Inc's proprietary TheraPlas® nonviral DNA delivery system, which is designed to safely transport the genetic material to the target site. Its primary goal is to activate both the innate and adaptive branches of the immune system, creating a broad and powerful anti-tumor response directly within the tumor microenvironment.

What was the purpose and design of the OVATION-2 trial?

The OVATION-2 study (NCT03393884) was a phase 1/2 clinical trial designed to assess the safety and efficacy of adding IMNN-001 to standard chemotherapy. The trial enrolled patients with newly diagnosed advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer. Patients were randomly assigned to 1 of 2 treatment groups:

1. Investigational Arm: Received IMNN-001 in combination with standard neoadjuvant/adjuvant chemotherapy (paclitaxel and carboplatin).

2. Control Arm: Received the standard chemotherapy regimen alone.

The primary measure of efficacy was progression-free survival (PFS), which is the length of time a patient lives without their disease getting worse. A key secondary endpoint was overall survival (OS), the gold standard for measuring a cancer therapy's clinical benefit.This carefully designed trial structure allowed for a direct comparison, providing clear data on the potential contribution of IMNN-001 to patient outcomes.

How effective was IMNN-001 in improving patient survival?

The OVATION-2 trial reported clinically meaningful improvements in both overall and progression-free survival for patients receiving IMNN-001.At a median follow-up of 31 months, patients in the IMNN-001 arm achieved a median overall survival (OS) of 46.0 months, compared with 33.0 months for those receiving chemotherapy alone (HR, 0.69; 95% CI, 0.40–1.19; P =.1865). This represents a clinically meaningful 13-month improvement, which an analyst report characterized as a 40% increase in median survival.

At a 24-month follow-up, the median progression-free survival (PFS) was 14.9 months for the IMNN-001 combination arm vs 11.9 months for the chemotherapy-alone arm (HR: 0.79; 95% CI, 0.51–1.23). This 3-month improvement indicates that the addition of IMNN-001 delayed the time to disease progression.

Commenting on these results, Premal Thaker, MD, a gynecologic oncologist at Siteman Cancer Center, noted that "the efficacy truly stands on its own, marking significant progress in drug development."

REFERENCES:

1. 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 September 24, 2025. https://tinyurl.com/57ddbbza

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 finalizes phase 3 study design with FDA for IMNN-001 in newly diagnosed advanced ovarian cancer. News release. IMUNON, Inc. March 24, 2025. Accessed September 24, 2025. https://tinyurl.com/mn4suw85

4. IMUNON Announces First Patient Dosed in Phase 3 OVATION 3 Study of IMNN-001 in Newly Diagnosed Advanced Ovarian Cancer. News release. IMUNON. July 30, 2025. Accessed September 24, 2025. https://tinyurl.com/y27rrcuk