Dr Thaker on Data for IMNN-001 Plus Neoadjuvant Chemotherapy in Newly Diagnosed Ovarian Cancer

"The good thing that we're seeing with this immunotherapy is that we haven't seen any cytokine release syndrome. We haven't seen any of the other [adverse] effects that have made it very hard for patients to receive [an agent targeting] IL-12, as they have previously."

Premal H. Thaker, MD, the David G. and Lynn Mutch Distinguished Professor of Obstetrics and Gynecology, director of Gynecological Oncology Clinical Research, and interim chief of the Division of Gynecologic Oncology at Siteman Cancer Center of Washington University in St. Louis, discussed updated findings from the phase I/II OVATION-2 trial (NCT03393884), which evaluated the safety and efficacy of the intraperitoneal IL-12 gene immunotherapy IMNN-001 in combination with neoadjuvant chemotherapy in patients with newly diagnosed, advanced epithelial ovarian cancer (EOC).

According to Thaker, earlier efforts to develop agents directed at IL-12 have been limited due to severe immune-related adverse effects, including cytokine release syndrome (CRS). IMNN-001 is intended to circumvent this limitation by delivering IL-12 intraperitoneally via a plasmid-based gene therapy, enabling a more favorable safety profile. Notably, no CRS or other high-grade immune toxicities were observed in this trial, according to data presented at the 2025 ASCO Annual Meeting.

The phase 2 portion of the study randomly assigned patients to receive standard-of-care (SoC) neoadjuvant chemotherapy with paclitaxel and carboplatin alone or in combination with IMNN-001. The updated analysis at 31 months of follow-up demonstrated that patients treated in the IMNN-001 arm (n = 58) achieved a median progression-free survival of 14.9 months compared with 11.9 months for chemotherapy along (HR, 0.79; 95% CI, 0.51-1.23; P = .2933). The median overall survival was 46.0 months vs 33.0 months, respectively (HR, 0.69; 95% CI, 0.40-1.19; P = .1865).

Further subgroup analysis indicated enhanced activity in patients with homologous recombination deficiency (HRD) and in those received maintenance PARP inhibitors. Among these patients, the median OS was not yet reached in the IMNN-001 arm (n = 19) compared with 37.1 months in the control arm (n = 24).

A phase 3 confirmatory trial (NCT06915025) is currently underway to evaluate the efficacy of IMNN-001 plus chemotherapy compared with neoadjuvant chemotherapy alone.