Perioperative IMNN-001 Utilizes Novel Delivery Route in Advanced Ovarian Cancer

Premal Thaker, MD

The intraperitoneal administration of IMNN-001—an interleukin-12 (IL-12)–directed gene therapy—could help address some of the safety concerns regarding with I-12–targeted drugs given intravenously, and this agent and method could provide another option in the up-dront, advanced epithelial ovarian cancer setting, according to ,c.

Findings from the phase I/II OVATION-2 trial (NCT03393884) presented at the 2025 ASCO Annual Meeting showed the addition of IMNN-001 to perioperative paclitaxel and carboplatin produced a median progression-free survival (PFS) of 14.9 months (95% CI, 12.55-21.19) compared with 11.9 months (95% CI, 10.09-14.92) in patients treated with chemotherapy alone (n = 54) at a median follow-up of 24 months (HR, 0.79; 95% CI, 0.51-1.23). Additionally, at a median follow-up of 31 months, the median overall survival (OS) was 46.0 months (95% CI, 39.20-NE) vs 33.0 months (95% CI, 27.14-not evaluable [NE]), respectively (HR, 0.69; 95% CI, 0.40-1.19; P = .1865).

“The efficacy [data from OVATION 2] stand on their own,” Thaker said. “It [is encouraging] to see that we’re moving the needle forward because that’s what anyone in drug development wants to do.”

In an interview with OncLive®, Thaker detailed the background for IMNN-001; explained how a peritoneal delivery method could address some of the AEs associated with IL-12–directed therapy given intravenously; and expanded on findings from OVATION-2.

Thaker is the David G. and Lynn Mutch Distinguished Professor of Obstetrics and Gynecology, director of Gynecological Oncology Clinical Research, and chief of the Division of Gynecologic Oncology at Washington University School of Medicine in St. Louis.

OncLive: What was the rationale for evaluating IMNN-001 in combination with standard perioperative chemotherapy in patients with ovarian cancer, given previous limitations with systemic IL-12 treatment?

Thaker: The standard of care in ovarian cancer has remained pretty much the same for up-front therapy. There's a lot of excitement about immunotherapy in a lot of cancer [types], but we have not made [much] headway in up-front ovarian cancer treatment with immune checkpoint inhibitors. Therefore, we need to look at different ways of optimizing the immune system and other ways to target the immune system.

OVATION-2 was built on the work of [the phase 1/2] OVATION-1 trial [NCT02480374], which was a study designed to determine] the appropriate dose [of IMNN-001] and evaluate whether it could be combined with chemotherapy.

OVATION-2 is a randomized, phase 2 trial where we look at taking women who are undergoing neoadjuvant chemotherapy—a standard of care—and randomly assigning them to [receive chemotherapy with or without IMNN-001 ], which is an intraperitoneal IL-12–directed immunotherapy that's given into the abdominal cavity, which is where this cancer is mainly housed.

[IMNN-001] is a way to try to target the immune system locally at the tumor microenvironment level without the systemic AEs…while giving patients standard-of-care chemotherapy. [Patients randomly assigned to the IMNN-001 arm] got the intraperitoneal therapy weekly [along] with neoadjuvant chemotherapy. [Patients received] 8 cycles of weekly treatment of IMNN-001 with chemotherapy vs standard of care chemotherapy [alone]. Then [patients] had interval debulking, followed by additional chemotherapy [with or without IMNN-001].

What was reported from this analysis at the 2025 ASCO Annual Meeting?

What we saw is that we [improved] PFS by 3 months. However, most importantly, we [improved] OS by 13 months. [These] are still not completely mature data, so we’re very optimistic that as the data continue to mature, we may see an even better OS, which is really what you want to see in an up-front therapy trial.

[Data from OVATION-2] led to [the phase 3] OVATION-3 trial [NCT06915025], which is a randomized trial that has just started. We’re hopeful that we will be able to replicate the same data and [validate it in] a bigger patient population [with a larger] sample size.

Additionally, we will [evaluate] the role of maintenance therapy, because while we were conducting OVATION-2, PARP inhibitors entered the world as maintenance. We saw that there’s a stronger [survival] signal [with the addition of IMNN-001] if patients received a PARP inhibitor. We want to see if we can build on that in the registrational OVATION-3 trial.

What should be known about the intraperitoneal delivery method for IMNN-001?

What we’ve learned in these trials is [how we can] help patients get more of the medication. We know intraperitoneal administration of medications can be a little harder for patients in terms of AEs, such as abdominal pain. Now we have ways of helping with pain control prophylactically, as opposed to waiting for a patient to have pain, and [we incorporated] some anxiety medicine to help.

The good thing that we’re seeing with [IMNN-001 is that] we haven’t seen any cytokine release syndrome. We haven’t seen any of the other AEs that have made it very hard for patients to receive IL-12. Previously, [it] used to be an intravenous injection, and it was abandoned in terms of development because of the AE profile.

We’re not seeing any of [those AEs] with the intraperitoneal therapy, and we [know] that we’re affecting both the adaptive and native immune systems. It’s important that we’re affecting a much bigger part of our immune system, as opposed to just T cells or natural killer cells. We’re getting macrophages—and everything—involved.

What was observed regarding safety and toxicity?

In terms of safety, there [were] more hematologic AEs [in the IMNN-001 arm], and that probably has a little bit to do with the oversampling in the trial, because when someone’s getting a weekly treatment, we [were] doing more blood samples on those patients compared with the standard-of-care arm.

The other [notable AE] would be abdominal pain. In the trial, we were able to give more patients this drug effectively [with prophylaxis]. One of the things that’s exciting is that we saw in this trial that IMNN-001, even if [patients were] not able to get the full 17 cycles; they still saw these robust effects. Most patients could only tolerate maybe 6 to 9 [doses of IMNN-001]. Hopefully, as we continue to gain more knowledge [and] do larger trials with these prophylactic medications, we’ll may see better improvements [in tolerance] and [administer] more medication into the patient.

Intraperitoneal chemotherapy was one of the National Cancer Institute alerts that we got in the early 2000s, and we have sort of fallen away from it because it is a little harder to administer, and we know that. However, we have seen this route be very efficacious for patients with ovarian cancer. I’m hopeful that the ovarian cancer community will re-engage in wanting to give this novel therapy via the abdomen, as opposed to intravenously.

Reference

Thaker P, Richardson D, Hagemann A, 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. J Clin Oncol. 2025;43(suppl 16):5516. doi:10.1200/JCO.2025.43.16_suppl.5516