Imunon's IMNN-001 Overcomes Historical IL-12 Safety Barriers in Phase 2 MRD Ovarian Cancer Data

Imunon announced new preliminary data from its ongoing phase 2 minimal residual disease (MRD) translational trial of IMNN-001, its DNA-based interleukin-12 (IL-12) gene immunotherapy, in combination with standard-of-care chemotherapy plus bevacizumab in women with newly diagnosed advanced ovarian cancer.¹ Among the first 18 patients to reach second-look laparoscopy, nine per arm out of a target enrollment of 30, patients treated with IMNN-001 showed a lower MRD-positive rate compared to control (44% versus 67%), a higher rate of circulating tumor DNA (ctDNA) clearance (87.5% versus 62.5%), and a numerically higher rate of patients achieving no evidence of disease following frontline therapy (100% versus 56%).¹

Stacy Lindborg, PhD, president and chief executive officer of Imunon, said in a press release, "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. 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."¹

Why does ctDNA clearance matter as a trial endpoint?

ctDNA has emerged as a prognostic biomarker for minimal residual disease across multiple cancer types, including ovarian cancer, with ctDNA positivity after treatment consistently associated with increased recurrence risk and inferior survival outcomes across pooled clinical data.² That growing body of evidence is part of why Imunon is tracking ctDNA clearance as a translational endpoint in the MRD study, alongside the trial's primary surgical MRD assessment, since a biomarker that can flag residual disease earlier and non-invasively could eventually complement or extend beyond what second-look laparoscopy alone can capture.²

That shift toward biomarker-driven precision oncology extends well beyond IL-12 immunotherapy. As Oren Gilad, PhD, president and CEO of Aprea Therapeutics, put it in a separate interview with BioPharm International, “The concept of personalized medicine has been proven in the clinic and on the market,” a dynamic reflected across drug classes as varied as ADCs, PARP inhibitors, and gene-based immunotherapies like IMNN-001.

How is the MRD trial designed?

The phase 2 MRD study (NCT05739981) is conducted through the Break Through Cancer Targeting Minimal Residual Disease in Ovarian Cancer TeamLab, a multi-institutional collaboration among Break Through Cancer's founding partner institutions, with the University of Texas MD Anderson Cancer Center serving as lead clinical site.¹ Patients in the experimental arm receive IMNN-001 intraperitoneally alongside neoadjuvant and adjuvant chemotherapy plus bevacizumab, followed by interval cytoreductive surgery and additional adjuvant cycles, then second-look laparoscopy to assess for minimal residual disease, followed by maintenance therapy assigned according to homologous recombination deficiency status.¹ The primary endpoint is MRD-positive rate at second-look laparoscopy, with progression-free survival as a secondary endpoint, alongside serial translational analysis of tumor tissue, ctDNA, microbiome, and intraperitoneal fluid.¹

Amir Jazaeri, MD, professor of gynecologic oncology and reproductive medicine at UT MD Anderson and the study's principal investigator, said, "These new findings from the MRD study add an important layer of evidence to what we've observed with IMNN-001 to date. 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."¹

IMNN-001 itself is built on Imunon's TheraPlas platform, an IL-12 DNA plasmid vector encased in a nanoparticle delivery system administered intraperitoneally, directly into the peritoneal cavity, the primary tumor environment in advanced ovarian cancer.^1,3 Consistent with that local, non-viral delivery approach, the MRD study has continued to show no cytokine release syndrome, systemic toxicities, or serious immune-related adverse events to date.¹

How does this fit Into IMNN-001's broader development program?

The MRD findings build on Imunon's completed Phase 2 OVATION 2 study, in which IMNN-001 was associated with a 14.7-month increase in median overall survival compared to chemotherapy alone (45.1 versus 30.4 months), extending to a 24.2-month increase among patients who also received PARP inhibitor maintenance therapy (65.6 versus 41.4 months).¹ IMNN-001 is now being evaluated in Imunon's pivotal Phase 3 OVATION 3 trial.¹ Epithelial ovarian cancer is the sixth deadliest malignancy among US women, with roughly 20,000 new cases annually and about 70% diagnosed at advanced stage III/IV, where five-year survival rates remain poor (41% and 20%, respectively) and recurrence after surgery and chemotherapy runs as high as 75%.¹

What happens next?

Lindborg said, "We remain focused on generating a comprehensive body of evidence for IMNN-001 across our clinical program. The MRD study, together with our Phase 2 OVATION 2 results and the ongoing pivotal Phase 3 OVATION 3 trial, continues to build a consistent picture of IMNN-001's benefit-risk profile in frontline ovarian cancer treatment."¹

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. (2026 Jul 21). GlobeNewswire. https://www.globenewswire.com/news-release/2026/07/21/3330491/0/en/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.html
2. Noronha MM, Gouveia MC, Costa de Almeida LF, et al. (2026 Jun). Prognostic value of circulating tumor DNA for minimal residual disease detection in ovarian cancer: A systematic review and meta-analysis. Gynecologic Oncology. https://www.sciencedirect.com/science/article/pii/S1040842826001873
3. Challener C. (2025 Dec 16). Achieving Targeted Delivery of Biologics with Nanoscale Systems. BioPharm International. https://www.biopharminternational.com/view/achieving-targeted-delivery-of-biologics-with-nanoscale-systems