IMNN-01 Plus Perioperative Chemo Improves OS in Newly Diagnosed, Advanced Ovarian Cancer

The addition of IMNN-001 to neoadjuvant and adjuvant chemotherapy with interval debulking or cytoreductive surgery led to an improvement in overall survival (OS) compared with standard-of-care (SOC) perioperative chemotherapy alone in patients with newly diagnosed, advanced ovarian cancer, according to topline data from the phase 2 OVATION 2 trial (NCT03393884).¹

Findings announced by IMUNON showed that in the intent-to-treat (ITT) population, those treated with IMNN-001 plus chemotherapy experienced an 11.1-month increase in median OS compared with those given SOC chemotherapy alone (HR, 0.74). Patients in the IMNN-001 arm also achieved a 3-month improvement in progression-free survival (PFS) vs those in the SOC arm (HR, 0.79).

Notably, approximately 90% of patients enrolled in either arm received at least 20% of the protocol-specified treatments, and in this population, IMNN-001 plus chemotherapy generated a 15.7-month increase in OS (HR, 0.64).

Additionally, nearly 40% of patients received a PARP inhibitor, and those in the IMNN-001 arm experienced a median OS that was not reached compared with 37.1 months for those in the control arm (HR, 0.41).

Full data from OVATION 2 will be presented at upcoming medical conference, and IMUNON expects to hold an end-of-phase 2 meeting with the FDA to determine protocols a phase 3 trial, which the company expects to initiate in the first quarter of 2025.

“These strong and clinically meaningful phase 2 results are highly encouraging, suggesting that IMNN-001 may improve the outcomes for women with advanced ovarian cancer. In the near term, we look forward to advancing our therapeutic into a phase 3 pivotal study as soon as possible,” Stacy Lindborg, PhD, president and chief executive officer of IMUNON, stated in a news release.¹ “Advancements in treatment options for advanced ovarian cancer in women who require neoadjuvant treatment have been limited over the years, and these patients continue to have poor prognoses. Our goal is for IMNN-001 to play an important role in the treatment regimen for the more than 300,000 women diagnosed with this deadly disease. On behalf of IMUNON, I extend heartfelt thanks to the women who participated in this trial, their families and the investigators.”

IMNN-001 is an interleukin-12 (IL-12) DNA plasmid vector held in a nanoparticle delivery system designed to enable cell transfection, leading to consistent, local secretion of IL-12.

OVATION 2 was a multicenter, open-label trial that enrolled patients who were at least 18 years of age with a histologic diagnosis of FIGO stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. Patients with the following histologies were allowed to enroll: high grade serous adenocarcinoma, endometrioid adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, or adenocarcinoma not otherwise specified.²

Other key inclusion criteria consisted of adequate bone marrow, renal, hepatic, and neurological function; and an ECOG performance status of 0 or 1. Patients receiving hormonal therapy directed at the primary tumor were required to discontinue treatment at least 1 week prior to first study treatment.

Patients were excluded if they received prior treatment with IMNN-001; received corticosteroids within 2 weeks of study entry or required ongoing systemic immunosuppressive therapy; received treatment for active autoimmune disease; received any prior radiotherapy to the abdominal cavity or pelvis; or had a history or evidence of central nervous system disease.

The study enrolled 112 patients who were randomly assigned 1:1 to receive IMNN-001 plus neoadjuvant and adjuvant chemotherapy, or SOC chemotherapy alone.¹ The chemotherapy regimen in both arms consisted of paclitaxel at 175 mg/m2 plus carboplatin at area under the curve 6 once every 3 weeks for a total of 6 cycles—3 as neoadjuvant therapy and 3 as adjuvant therapy. In the experimental arm, patients also received IMNN-001 at 100 mg/m2 on days 8 and 15 of the first cycle of chemotherapy, then on days 1, 8, and 15 of subsequent cycles for a total of 17 doses.^1,2

PFS served as the trial’s primary end point.² Notably, as a phase 2 study, OVATION 2 was not powered for statistical significance.¹ Secondary end points included objective response rate, chemotherapy response score, and surgical response.

“It is highly gratifying to witness the extraordinary overall survival benefit that IMNN-001 showed in this phase 2 study further supported by consistency across data, including in PFS and in the patients who received 3 doses or more of IMNN-001 gaining an additional 15.7 months of life, while the safety profile was tolerable,” Sebastien Hazard, MD, chief medical officer of IMUNON, added in a news release.¹ “It suggests that IMUNON’s IL-12 gene therapy has a long-term impact on the disease.”

References

1. IMUNON announces 11.1 month increase in overall survival in patients with newly diagnosed, advanced ovarian cancer treated with IMNN-001. News release. IMUNON. July 30, 2024. Accessed July 30, 2024. https://investors.imunon.com/news-releases/news-release-details/imunon-announces-111-month-increase-overall-survival-patients
2. Study of IMNN-001 (also known as GEN-1) with NACT for treatment of ovarian cancer (OVATION 2). ClinicalTrials.gov. Updated July 30, 2024. Accessed July 30, 2024. https://clinicaltrials.gov/study/NCT03393884