Imunon, Inc. is advancing its lead drug candidate, IMNN-001, towards a Phase 3 clinical trial for patients with advanced ovarian cancer, slated to begin in the first quarter of 2025. The decision follows encouraging results from the Phase 2 OVATION-2 trial, which demonstrated a clinically significant improvement in overall survival (OS) when IMNN-001 was combined with standard chemotherapy.
OVATION-2 Trial Results
The OVATION-2 trial (NCT03393884) revealed that patients treated with IMNN-001 plus chemotherapy experienced a median OS of 40.5 months, compared to 29.4 months for those receiving chemotherapy alone (HR, 0.74; 95% CI, 0.42-1.30; P = .2963). These findings, presented at the 2024 SITC Annual Meeting, suggest a potential benefit of over 11 months in survival for the combination therapy.
Premal Thaker, MD, MS, director of Gynecological Oncology Clinical Research at Siteman Cancer Center, noted the clinical meaningfulness of the survival extension, stating it represents "a whole year of birthdays, holidays, and everything else that they’re able to do."
Notably, a subset of patients who received a PARP inhibitor, regardless of IMNN-001 exposure, showed a median OS that was not reached in the experimental arm, compared to 37.1 months in the control arm (HR, 0.41; 95% CI, 0.13-1.28), indicating a potential synergistic effect.
Mechanism of Action and Safety
IMNN-001 is a DNA immunotherapeutic designed to deliver interleukin (IL)-12 directly to the tumor microenvironment. IL-12 is a potent pro-inflammatory cytokine known to activate T cells and natural killer cells, promote interferon-gamma production, and modulate myeloid-derived suppressor cells. The localized delivery aims to maximize immune stimulation while minimizing systemic toxicity, a common challenge with systemic IL-12 therapies.
According to Imunon, IMNN-001 leads to a sustained increase in IL-12 levels at the tumor site without causing systemic increases, thereby reducing the risk of cytokine release syndrome. The use of a DNA plasmid ensures sustained IL-12 expression over several days, offering an advantage over recombinant IL-12 infusions and mRNA therapies with shorter expression times.
While the experimental arm experienced increased gastrointestinal adverse effects, investigators found that these could be effectively managed with appropriate pain management protocols. No significant immune-related adverse events were reported.
Addressing Unmet Needs in Ovarian Cancer
Dr. Thaker emphasized the potential of IMNN-001 to address unmet needs in ovarian cancer treatment, particularly for patients who are not candidates for complete upfront surgical removal of the tumor. She highlighted that IMNN-001 could help "rev up" the innate and adaptive immune systems, potentially leading to better surgical outcomes and overall survival benefits.
IMNN-001's unique mechanism of action, combined with its manageable safety profile, positions it as a promising candidate for further investigation in a Phase 3 trial. The trial aims to confirm the OVATION-2 findings and potentially establish a new standard of care for patients with advanced ovarian cancer.
