ASCO Conference Coverage

IMNN-001 Plus Neoadjuvant Chemotherapy Shows Promising Survival Benefit in Advanced Ovarian Cancer

Kate Young

Key Highlights

  • IMNN-001 in combination with neoadjuvant chemotherapy improved median overall survival from 33 to 46 months in advanced epithelial ovarian cancer.
  • Median progression-free survival increased by 3 months in the experimental arm (14.9 vs 11.9 months).
  • IMNN-001 was well tolerated, with no evidence of cytokine release syndrome or increased immune-related adverse events.
  • Enhanced response outcomes were observed, particularly in patients receiving PARP inhibitors and those with homologous recombination deficiency+ status.

A phase I/II trial (OVATION-2) evaluating the addition of intraperitoneal IMNN-001, an interleukin-12 (IL-12) gene therapy, to standard neoadjuvant chemotherapy (NACT) in newly diagnosed advanced epithelial ovarian cancer (EOC) patients demonstrated promising early indications of clinical benefit. This study was presented at the American Society of Clinical Oncology 2025 Annual Meeting.

The study observed a favorable trend in both progression-free survival (PFS) and overall survival (OS) for the IMNN-001 combination therapy group. Median OS improved by 13 months (46.0 vs 33.0 months; HR = 0.69), and median PFS by 3 months (14.9 vs 11.9 months; HR = 0.79), despite the trial not being powered for statistical significance. Totality of Evidence (ToE) analyses showed 6.5 months of reduced time lost due to progression or death.

Epithelial ovarian cancer is a highly lethal gynecologic malignancy with high recurrence rates, underscoring the need for new therapeutic approaches that enhance the efficacy of existing standard-of-care treatments. IMNN-001, a novel IL-12 gene therapy designed to augment immune-mediated anti-tumor activity, was evaluated in this context to determine its potential to improve clinical outcomes when added to traditional chemotherapy.

In this randomized, controlled, multicenter study (NCT03393884), 112 patients were randomized 1:1 to receive either NACT alone or NACT combined with IMNN-001. Both arms received IV carboplatin/paclitaxel every 21 days for three cycles before and after interval debulking surgery (IDS). The experimental arm additionally received intraperitoneal IMNN-001 weekly for 8 weeks pre-IDS and 9 weeks post-IDS. Primary and secondary endpoints included PFS, OS, chemotherapy response score (CRS), surgical response score (SRS), and overall response rate (ORR). The data cut-off for PFS was June 2024 and for OS was November 2024.

The IMNN-001 arm included patients with a higher proportion of stage IV disease (31.0% vs 22.2%) and ECOG PS greater than or equal to 1 (48.3% vs 35.2%) yet showed better outcomes. Fewer patients in the experimental group received maintenance PARP inhibitors (32.8% vs 44.4%) despite comparable HRD status. IMNN-001 was well tolerated, with the most common adverse events being abdominal pain, nausea, and vomiting. No cases of cytokine release syndrome or increased immune-related toxicity were reported. Improved CRS and SRS outcomes were observed in the experimental arm. Among patients treated with PARP inhibitors, the median PFS was 33.8 vs 22.1 months, and median OS was not reached in the IMNN-001 arm versus 37.1 months in controls.

“IMNN-001 demonstrated trends towards material improvement in overall survival and acceptable safety in advanced EOC, especially in HRD+ patients,” the study authors concluded. “These results are supportive of further development in the upcoming pivotal phase 3 study.”

Reference:
Thaker PH, Richardson DL, Hagemann AR, et al. A phase I/II study of the safety and efficacy of intraperitoneal IMNN-001 in combination with neoadjuvant chemotherapy (NACT) of paclitaxel and carboplatin in patients newly diagnosed with advanced epithelial ovarian cancer (EOC): Updated survival analysis from OVATION-2 trial. Presented at: ASCO Annual Meeting; May 30–June 3, 2025; Chicago, IL. https://www.asco.org/annual-meeting