IMNN-001 Plus Chemo Cuts MRD Rate in Frontline Ovarian Cancer

Adding the IL-12 immunotherapy IMNN-001 to standard neoadjuvant and adjuvant chemotherapy plus bevacizumab (Avastin) showed a lower rate of minimal residual disease (MRD), higher circulating tumor DNA (ctDNA) clearance, and a numerically higher rate of no evidence of disease (NED) compared with chemotherapy plus bevacizumab alone in women with newly diagnosed advanced ovarian cancer, according to preliminary data from an ongoing phase 2 MRD translational study (NCT05739981).¹

Nine patients in each of the control and experimental arms of the study have reached second-look laparoscopy (SLL), the study's primary assessment point for surgical MRD evaluation. Among these patients, the MRD-positive rate was 44% in the IMNN-001 arm compared with 67% in the control arm, and the rate of ctDNA clearance was 87.5% with IMNN-001 vs 62.5% with control.¹ A numerically higher proportion of patients in the IMNN-001 arm achieved NED following frontline therapy compared with control (100% vs 56%). The study's total target accrual is 30 patients, with 15 planned per arm, and these results represent preliminary data from the ongoing study.

These findings add a new layer of translational evidence to results previously reported from the completed phase 2 OVATION 2 study (NCT03393884), in which IMNN-001 plus standard-of-care neoadjuvant and adjuvant chemotherapy produced a 14.7-month improvement in median overall survival compared with chemotherapy alone in 112 patients with newly diagnosed advanced ovarian cancer (45.1 vs 30.4 months). Among patients who also received PARP inhibitor maintenance therapy, the median OS separation widened to 24.2 months (65.6 vs 41.4 months).1 The OVATION 2 results also showed a 35% improvement in OS (HR, 0.74) and a 25% improvement in progression-free survival (PFS) vs standard care alone.²

In addition to efficacy results, new translational data from the MRD study continue to support IMNN-001's proposed mechanism of action, with the agent inducing robust expression of IL-12 in macrophages within peritoneal fluid and tumor tissue, stimulating a cascade of anti-tumor cytokines including interferon-gamma, and resulting in potent macrophage and T cell activation, findings consistent with a shift in the tumor immune microenvironment from immunologically cold to hot.¹

"These new findings from the MRD study add an important layer of evidence to what we've observed with IMNN-001 to date," Amir Jazaeri, MD, professor of Gynecologic Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Center and the study's principal investigator, stated in the news release.¹ "The reduction in residual disease and the encouraging ctDNA clearance we're seeing, together with a consistent safety and tolerability profile, strongly support the continued investigation of IMNN-001's role in the frontline treatment of ovarian cancer."

Safety of IMNN-001

The favorable tolerability profile of IMNN-001 observed in prior studies has been sustained in the MRD study, including when used in combination with standard chemotherapy plus bevacizumab and in the maintenance setting. No cytokine release syndrome, systemic toxicities, or serious immune-related adverse events have been observed to date.1 This safety profile is notable given the historical challenges associated with systemic IL-12 administration, which have limited the clinical development of IL-12-based therapies in oncology; IMNN-001's intraperitoneal, DNA-plasmid delivery approach is designed to achieve local cytokine production while avoiding the systemic toxicities seen with recombinant IL-12.¹

Study Design and Patient Population

The phase 2 MRD study is a translational clinical trial evaluating IMNN-001 in combination with standard-of-care neoadjuvant and adjuvant chemotherapy plus bevacizumab in women with newly diagnosed advanced ovarian cancer. The study is being conducted through the Break Through Cancer Targeting Minimal Residual Disease in Ovarian Cancer TeamLab, a multi-institutional collaboration led by The University of Texas MD Anderson Cancer Center as the primary clinical site.

Patients in the experimental arm receive IMNN-001, administered intraperitoneally, in combination with neoadjuvant and adjuvant chemotherapy plus bevacizumab, followed by interval cytoreductive surgery and additional adjuvant cycles. Following chemotherapy, patients undergo SLL to assess for MRD, then proceed to maintenance therapy assigned based on homologous recombination deficiency status. The primary end point is MRD-positive rate at SLL; secondary end points include PFS. The study also incorporates serial translational analyses of tumor tissue, ctDNA, microbiome, and intraperitoneal fluid to further characterize IMNN-001's immunological impact.

IMNN-001 is currently being evaluated in the pivotal phase 3 OVATION 3 trial in patients with newly diagnosed advanced ovarian cancer at clinical sites across the United States.¹

"We are encouraged by these new data points from our MRD study, which continue to build the case for IMNN-001's potential to make a meaningful difference for women with newly diagnosed advanced ovarian cancer," Stacy Lindborg, PhD, president and chief executive officer of IMUNON, stated in the news release.¹ "These findings, together with the consistent safety profile we've now observed across multiple studies, reinforce that we have overcome the historical safety and efficacy barriers associated with the development of a novel IL-12 immunotherapy and further bolster our confidence in IMNN-001 as we continue to advance our pivotal phase 3 OVATION 3 trial."

References

1. IMUNON reports positive phase 2 MRD clinical data for IMNN-001, demonstrating the successful overcoming of historical IL-12 safety barriers in frontline ovarian cancer. News release. IMUNON Inc. July 21, 2026. Accessed July 21, 2026. https://investors.imunon.com/news-releases/news-release-details/imunon-reports-positive-phase-2-mrd-clinical-data-imnn-001

2. IMUNON presents positive data from phase 2 OVATION 2 clinical trial of IMNN-001 in advanced ovarian cancer at SITC 39th Annual Meeting. News release. IMUNON Inc. November 7, 2024. Accessed July 21, 2026. https://investors.imunon.com/news-releases/news-release-details/imunon-presents-positive-data-phase-2-ovation-2-clinical-trial