Dr Thaker Highlights Survival Benefit With IMNN-001 in Ovarian Cancer

The investigational agent IMNN-001 is demonstrating promising potential to extend survival in patients with advanced ovarian cancer, a population where achieving long-lasting benefit has traditionally been challenging.

A recently reported update from the phase 2 OVATION 2 trial (NCT03393884) showed that adding IMNN-001 to standard of care (SOC) chemotherapy improved the median overall survival (OS) by 14.7 months vs SOC chemotherapy alone in women with newly diagnosed advanced ovarian cancer.¹ Of note, this median OS benefit extended to 24.2 months among a subgroup of patients who also were treated with a PARP inhibitor as part of a maintenance therapy regime.

In an interview with Targeted Oncology, Premal Thaker, MD, MS, chair of OVATION 2 as well as the ongoing phase 3 OVATION 3 trial (NCT06915025), discussed the mechanism of IMNN-001, the OVATION 2 results, and next steps with IMNN-001 and immunotherapy in ovarian cancer. Thaker is chief of Gynecologic Oncology, David & Lynn Mutch Distinguished Professor of Obstetrics & Gynecology, director of Gynecologic Oncology Clinical Research at Washington University School of Medicine.

Targeted Oncology: The TheraPlas platform drives locoregional IL-12 secretion intraperitoneally. How does the sustained, localized cytokine expression differ mechanistically from systemic IL-12 approaches that historically showed significant toxicity, and what does the tumor microenvironment look like after treatment?

Premal Thaker MD, MS: The key difference to this molecule is its platform of how it's administered and how it's a plasmid that allows us to administer IL-12 to the tumor microenvironment and avoid all the systemic effects that had been seen previously from recombinant humanized IL-12. This is novel in the sense that it is incorporated into a DNA plasmid, and therefore by the mechanism, avoids augmenting that cytokine pathway in terms of a systemic approach, but it does it very much in the local tumor microenvironment. And so it gives a sustainable way for tumors to end up having memory and sort of being persistent in the cavity for enough time to sort of give that education of our adaptive and innate immune systems.

The 24.2-month OS benefit in patients who received PARP inhibitors is nearly double the benefit seen without them. Do you believe this is a true synergistic immunologic interaction, or is it largely additive, and what's the hypothesis driving that combination?

When the OVATION-2 trial was developed, we did not have the knowledge of PARP inhibitors being beneficial for patients with HRD or BRCA mutations, and we know patients who have HRD somatic mutations within the tumor or BRCA mutations have an inability to repair their DNA, and so when you have more neoantigens that also will stimulate your immune system to try to learn how to attack cancer cells, because it's having a sort of what we call “more inflamed” signature. And that is probably how having IL-12, in addition to the patients who have gotten a PARP inhibitor, have seen this much more sustained benefit. So hopefully the OVATION-3 trial will be looking at that in much more detail, because we'll be knowing the patient's molecular signatures ahead of time, as well as knowing that we'll be following those patients specifically with their PARP inhibitor usage as well.

You noted there have been no meaningful SOC advances in ovarian cancer in three decades. For oncologists who are cautiously optimistic but have seen many promising phase 2 results fail to replicate, what is most different about this data and this mechanism that gives you confidence the OVATION 3 trial will confirm what you're seeing?

The part that gives me a lot of confidence, the difference is, how are we attacking the immune system? We're not just focusing, as we do, like on checkpoint inhibitors that made a huge splash in many cancers. We're not just looking at T cells. This actually will change NK cells, T cells, in the tumor microenvironment. And that's based on our phase 1 data that we had that we could really see a change in the samples before treatment versus once they had been treated with chemotherapy and this compound of IMNN-001, this is much more of a more global cytokine that affects your immune system. 

With bevacizumab and PARP inhibitors already embedded in frontline ovarian cancer treatment, where does IMNN-001 practically fit, and does it require any modification of existing chemotherapy sequencing?

It really doesn't change the process, because right now the one thing that we have not tested in this trial is the addition of using bevacizumab upfront, which is an antiangiogenic with chemotherapy, which hasn't changed for 30 years. How this would be different is the fact that it does require the weekly administration, but we give lots of chemotherapy drugs weekly, and we can still offer patients their normal maintenance therapy. We have a different trial that's sort of looking at the safety of IMMN-001, with bevacizumab to see about that. However, I would also caution that with the use of bevacizumab, we have not seen an OS benefit in those patients, and we see a very similar progression-free survival benefit that we see with IMMN-001, at approximately 3.5 or 3.8 months. You're not really gaining much of a benefit by adding the bevacizumab.

The OS benefit is what patients want. They don't want to know that they're living 3 extra months before their next recurrence. They want to really know that they have over a year or more extra life. And that's what we see with immunotherapy. It gives us much more of a prolonged, durable effect, as opposed to a short-term gain. It's not a sprint, it's a marathon of teaching your immune system how to react and keep that sort of cancer recurrence under suppression, or to at least if you do recur, potentially have more augmentation of your immune system to fight it the next time.

REFERENCES

1. IMUNON, Inc. IMUNON reports updated phase 2 data showing continued improvement in median overall survival with IMNN-001 in women with newly diagnosed advanced ovarian cancer. March 25, 2026. Accessed April 24, 2026. https://tinyurl.com/3sj5we7n

2. IMUNON Phase 3 OVATION 3 study. ClinicalTrials.gov. Updated April 13, 2026. Accessed April 24, 2026. NCT06915025. https://clinicaltrials.gov/study/NCT06915025