IMNN-001/Chemo Improves Survival in Advanced Ovarian Cancer

"If confirmed in a phase 3 clinical trial, IMNN-001 could reset the standard of care for [patients] with ovarian cancer," according to Premal H. Thaker, MD.

Administering the DNA-mediated immunotherapy IMNN-001 in combination with neoadjuvant and adjuvant chemotherapy (NACT) improved overall survival (OS) compared with NACT alone among patients with advanced ovarian cancer, according to data from the phase 2 OVATION 2 study (NCT03393884).¹

Frontline treatment with IMNN-001 plus NACT extended the median OS by 11.1 months compared with NACT only across the trial’s intent-to-treat (ITT) population (HR, 0.74). Of approximately 90% of patients who were treated with 20% or more of the specified treatments based on protocol, OS increased by 15.7 months in the IMNN-001 arm (HR, 0.64). Additionally, approximately 40% of the population received a PARP inhibitor; in this subgroup, the median OS was not reached with IMNN-001 plus NACT vs 37.1 months with NACT alone (HR, 0.41).

These OS outcomes are supported by the progression-free survival (PFS) results. Treatment with IMNN-001 plus NACT prolonged PFS by 3 months compared with NACT only (HR, 0.79).¹

Developers intend to initiate an end-of-phase 2 meeting with the FDA to support a phase 3 study of IMNN-001 in this patient population. This phase 3 study is expected to launch in the first quarter of 2025. Additionally, investigators look to present detailed results from OVATION 2 at a future medical meeting and submit their findings for publication in a peer-reviewed medical journal.

“Typically, an increase in survival of 6 months is considered to be clinically meaningful, and extending survival from 29 months with standard-of-care treatment to 40 months with the addition of IMNN-001 is compelling. Importantly, the extension of survival among [patients who received] IMNN-001 also exposed to the new standard that includes PARP inhibitors is even greater,” study chair Premal H. Thaker, MD, interim chief of Gynecologic Oncology, a David & Lynn Mutch Distinguished Professor of Obstetrics & Gynecology, and director of Gynecologic Oncology Clinical Research at Washington University School of Medicine, stated in the press release about the data.¹ “If confirmed in a phase 3 clinical trial, IMNN-001 could reset the standard of care for [patients] with ovarian cancer.”

IMNN-001 is an investigational interleukin-12 (IL-12) DNA plasmid vector encased in a nanoparticle delivery system, which can facilitate local secretion of the IL-12 protein. Developers hypothesize that IL-12 is one of the most active cytokines for inducing potential anticancer immunity via T-lymphocyte induction and natural killer cell proliferation.

In the open-label, multicenter OVATION 2 trial, patients were randomly assigned to receive standard NACT with or without IMNN-001. NACT consisted of carboplatin at area under the curve 6 intravenously plus paclitaxel at 175 mg/m² intravenously.²

The trial’s primary end point was PFS. Other end points included objective response rate, chemotherapy response score, and surgical response. The trial was not powered for statistical significance due to its phase 2 design.

Patients 18 years and older with histologically diagnosed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma and International Federation of Gynecology and Obstetrics stage III or IV disease were eligible for enrollment on the trial. Other eligibility criteria included having adequate bone marrow, renal, hepatic, and neurologic function.

Investigators previously completed the dose-escalation phase 1b OVATION 1 study (NCT02480374) assessing IMNN-001 plus carboplatin/paclitaxel for patients with newly diagnosed ovarian cancer.

“[We] have been investigating IMNN-001 since the phase 1 OVATION 1 study and continue to be frustrated by the lack of substantial progress in primary treatment options available to treat this disease. The results from this trial demonstrating that IMNN-001 could extend life by one year or longer are provocative and powerful. I believe that should efficacy be confirmed in a pivotal study, IMNN-001 will be quickly incorporated into the care regimen,” concluded lead trial investigator Charles A. Leath, III, MD, director in the Division of Gynecologic Oncology, Ellen Gregg Shook Culverhouse Chair in Gynecologic Oncology, and professor in the Department of Obstetrics and Gynecology at the University of Alabama Medical Center.¹

References

1. IMUNON announces 11.1 month increase in overall survival in patients with newly diagnosed, advanced ovarian cancer treated with IMNN-001. News release. Imunon, Inc. July 30, 2024. Accessed July 31, 2024. https://tinyurl.com/39cmpyea
2. Study of IMNN-001 (also known as GEN-1) with NACT for treatment of ovarian cancer (OVATION 2) (OVATION 2). ClinicalTrials.gov. Accessed July 31, 2024. https://tinyurl.com/2ewsjy27