IMNN-001/Chemo Displays TME Shift in Newly Diagnosed Ovarian Cancer

IMNN-001 plus chemotherapy exhibited improved efficacy and produced key anti-cancer immune cytokines after treatment in patients with advanced newly diagnosed ovarian cancer, according to a news release from the drug’s developer, IMUNON, Inc.¹ The news release was based on findings from the phase 2 OVATION 2 trial (NCT03393884) presented at the American Association for Cancer Research (AACR) Special Conference in Cancer Research: Advances in Ovarian Cancer Research.²

Specifically, a positive shift in the tumor microenvironment (TME) was observed, increasing the ratio of immune stimulatory T cell ratios in most patients treated with the agent, including CD8-positive or T regulatory cells, CD8-positive or IDO-positive cells, and CD8-positive or CD4-positive cells. Additionally, a shift favoring a decrease in immunosuppression cells, including IDO-positive, PD-L1-positive, CD4-positive, and T regulatory cells, and an increase in CD8-positive, CD8-positive effector, and myeloid dendritic cells was reported in most patients following treatment.

The developers also noted that IMNN-001 created a “hot” anti-TME effect through the increased recruitment of anti-tumor CD8-positive and myeloid dendritic cells in 50% to 80% of paired samples as well as the decreased presence of immunosuppressive biomarkers—namely IDO, PD-L1, and T regulatory cells—in 65% to 80% of samples. Furthermore, the investigational agent appeared to show a prolonged favorable safety profile among these patients.

“These new translational data are encouraging and…are consistent with the unprecedented positive overall survival [OS] results previously reported from the OVATION 2 study,” Douglas V. Faller, MD, PhD, chief medical officer of IMUNON and study presenter at the AACR conference, said in the news 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 [TME] from ‘cold’ to ‘hot’ by activating both innate and adaptive immune systems, with limited to no systemic toxicities.”

Patients with newly diagnosed advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer were enrolled on the study (n = 112) and randomly assigned 1:1 to receive either IMNN-001 plus neoadjuvant/adjuvant chemotherapy consisting of paclitaxel and carboplatin or chemotherapy alone. Patients were treated in the neoadjuvant setting to shrink tumors for optimal resection following 3 cycles of chemotherapy.

Following debulking, patients underwent 3 additional cycles of adjuvant chemotherapy to treat residual tumors. Patients assigned to the investigational arm received 100 mg/m² of IMNN-001 for a maximum of 17 weekly doses.

The primary end point of the study was progression-free survival (PFS).³ OS was a secondary end point. In the translational analysis, immune marker expression in tumors were analyzed in pre- and post-treatment tissue samples analyzed by cyclic immunofluorescence analysis.

Additionally, the phase 3 OVATION 3 trial (NCT06915025)in advanced epithelial ovarian cancer was initiated in July 2025 and supported by survival data from the phase 2 study.⁴ In the phase 2 study, a median 13-month increase in OS (HR, 0.70) and a median 3-month increase in PFS (HR, 0.79) were observed with IMNN-001 vs standard of care alone. Enrollment for the OVATION 3 trial is ongoing at 4 sites, with 46 additional sites considered for activation.

“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. 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 concluded.¹

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, Inc. September 22, 2025. Accessed September 23, 2025. https://tinyurl.com/3swkmedy
2. Anwer K, Sood S, Musso L, et al. IMNN-001, an IL-12 gene therapy added to Neo/Adjuvant chemotherapy safely turns the tumor microenvironment cold-to-hot in newly diagnosed epithelial ovarian cancer. Presented at American Association for Cancer Research (AACR) Special Conference in Cancer Research: Advances in Ovarian Cancer Research; September 19-21, 2025; Denver, CO. Abstract B050
3. Study of IMNN-001 also known as GEN-1) with NACT for treatment of ovarian cancer (OVATION 2) (OVATION 2). ClinicalTrials.gov. Updated September 5, 2025. Accessed September 23, 2025. https://tinyurl.com/3nuy4yjv
4. Phase 3 trial evaluating the safety & efficacy of IMNN-001 administered in combination w/​ standard NACT & adjuvant chemotherapy in newly diagnosed patients w/​ advanced EOC, fallopian tube or primary peritoneal cancer (OVATION-3). ClinicalTrials.gov. Updated September 5, 2025. Accessed September 23, 2025. https://tinyurl.com/4z56abj2