IMNN-001 Plus Chemo Data Highlight Potential to Fill Unmet Need in Ovarian Cancer

Premal Thaker, MD, MS

Findings from the phase 2 OVATION-2 trial (NCT03393884) showing an 11.1-month improvement in overall survival (OS) with the IL-12 immunotherapy IMNN-001 plus chemotherapy vs chemotherapy alone have given hope to investigators that the combination may be a safe and efficacious option for patients with newly diagnosed advanced epithelial ovarian cancer, according to Premal Thaker, MD, MS.¹

“Based on these very exciting results, we’re hopeful that we’ll be able to perform a phase 3 trial so we can replicate [these findings] and also get more patients on trial so [that] we may get a new medication to market for patients,” Thaker said in an interview with OncLive®. “I’m very encouraged. Drug development is very hard, as all of us know, but it’s very exciting when we see results that hopefully can move the standard of care [forward] because all of us want to get better treatments for our patients.”

The developer of IMNN-001, which is a DNA plasmid vector encased in a nanoparticle delivery system, noted that they plan to initiate a pivotal phase 3 clinical trial in the first quarter of 2025.² Findings presented at the 2024 SITC Annual Meeting showed that at a median follow-up of 24 months, patients treated with the doublet (n = 58) experienced a median OS of 40.5 months (95% CI, 28.09-NE) vs 29.4 months (95% CI, 24.94-45.60) among those treated with chemotherapy alone (n = 54; HR, 0.74; 95% CI, 0.42-1.30; P = .2963).¹ Additionally, patients who received a PARP inhibitor regardless of exposure to IMNN-001 during treatment (n = 74) experienced a median OS of not reached in the experimental arm compared with 37.1 months in the control arm (HR, 0.41; 95% CI, 0.13-1.28).

Furthermore, gastrointestinal adverse effects (AEs) were increased in the experimental arm, and investigators noted that pain management protocols were effective in the study. No AEs of special interest or serious immune-related AEs occurred.

In the interview, Thaker highlighted key data derived thus far with IMNN-001 and its potential to fill an unmet need for patients with ovarian cancer. She also detailed considerations when targeting IL-12 and how IMNN-001 has shown the potential to do so in a subsequent article. Thaker is 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 in Saint Louis, Missouri.

OncLive: What data were seen with IMNN-001 plus chemotherapy in OVATION 2?

Thaker: In our phase 2 trial looking at IMNN-001 [plus] neoadjuvant chemotherapy vs neoadjuvant chemotherapy [alone], we saw an 11.1-month improvement in OS in the all-comers population. However, if patients were able to get at least 20% of the recommended doses of IMNN-001, that [improvement] rose to over 15 months. If you talk to patients, that’s clinically meaningful—that’s a whole year of birthdays, holidays, and everything else that they’re able to do.

We also saw an interesting [efficacy] signal [for the combination] in our patients who had [received a prior PARP inhibitor], who didn’t reach [a median] OS. We’re seeing that there might be some synergism.

What safety data have been observed thus far with the agent?

The safety data that we saw [showed increased] abdominal discomfort, and that happens with intraperitoneal therapies because there’s a physical distension of the cavity that causes a pain issue sometimes. During the trial, we were able to then come up with a way to prevent that by giving pain medications so that patients were able to tolerate the treatment.

We also saw a bit more myelosuppression, but we were also doing more laboratories for the patients who were getting the weekly treatments compared with the standard neoadjuvant chemotherapy treatments, where they were getting only laboratories every 3 weeks [vs every 1 week for the experimental arm]. Chemotherapy causes nadir, so I don’t believe all of it was from IMNN-001; it was just that we were overtesting that population. It was a very tolerable [therapy]. There was some nausea [that occurred], but that could be easily overcome with [supportive] medication.

How could IMNN-001 fill an unmet need for patients with ovarian cancer?

Patients who get neoadjuvant chemotherapy tend to be our sicker patients, and [they] are the patients in whom we don’t think we can remove all the cancer up-front; we know their biology seems to be different because their spread of cancer is different. We need some way to have the innate and adaptive immune systems rev up in a sense of getting interferon-γ and all these other cytokines to help with the tumor immunosuppressive environment being changed.

This is a huge improvement because we saw the patients who received IMNN-001 also had better surgical outcomes, which seems to also parlay the exciting OS benefits. We haven’t changed the [up-front] paradigm in a very long time for ovarian cancer—we’ve done [so] in the maintenance [setting]—but this is an all-comer treatment because we had a lot of patients who also [had] homologous repair-proficient [disease who] are the harder-to-treat patients.

What would you like your colleagues to take away from this research?

The most important thing is not to give up on immunotherapy because we’ve all seen a lot of negative trials with checkpoint inhibitors [in ovarian cancer]. We’ve had a lot of patients on trials because we’re all very optimistic people in oncology and we want to find the next best [treatment]. This [strategy with IMNN-001] harnesses immunotherapy because we’re targeting many different aspects, and IL-12 is important in anti-angiogenesis. [IMNN-001] is not just immunotherapy; it’s also helping with anti-angiogenesis which is very important because there are lots of drugs like bevacizumab [Avastin] or other anti-angiogenic drugs that we use commonly in ovarian cancer.

IL-12 is a very potent cytokine, and it’s key that we all appreciate that [IMNN-001] is not just immunotherapy or anti-angiogenic therapy. It’s a way to target the ovarian cancer environment along with chemotherapy very effectively.

I’ve been working with this molecule, IMNN-001, in platinum-resistant disease through phase 1 and phase 2, and hopefully soon phase 3 [trials]. One of my mentors always talks about how many years and decades [drug development] takes, and I’m at over a decade with this molecule. I’m very excited to see it’s progression because sometimes you have to tweak things to find where the right niche is for drug development, and it seems like this is the appropriate place where it’s [being used in] the up-front [setting]. That makes more sense because in a lot of cancers, we’re understanding that the immune system gets exhausted with more treatments, so the earlier we expose patients to these types of novel agents [the more likely it is] that they can develop an immune memory for their body to be able to continue to have a better outcome. That’s probably what we’re seeing with the OS [data], which is what we’re hoping for.

References

1. Thaker PH, Richardson DL, Hagemann AR, et al. Phase I/II study of safety and efficacy of intraperitoneal IMNN-001 with neoadjuvant chemotherapy of paclitaxel and carboplatin in patients newly diagnosed with advanced epithelial ovarian cancer. Presented at: 2024 SITC Annual Meeting; November 6-10, 2024; Houston, TX. Abstract 1505.
2. IMUNON presents positive data from phase 2 OVATION 2 clinical trial of IMNN-001 in advanced ovarian cancer at SITC 39th Annual Meeting. News Release. IMUNON. November 7, 2024. Accessed November 26, 2024. https://www.globenewswire.com/news-release/2024/11/07/2976849/0/en/IMUNON-Presents-Positive-Data-from-Phase-2-OVATION-2-Clinical-Trial-of-IMNN-001-in-Advanced-Ovarian-Cancer-at-SITC-39th-Annual-Meeting.html