IMNN-001 Plus Perioperative Chemotherapy Maintains OS Benefit in Newly Diagnosed Advanced Ovarian Cancer

Updated results from the phase 2 OVATION 2 trial (NCT03393884) continued to show an overall survival (OS) benefit with the addition of IMNN-001 to neoadjuvant and adjuvant chemotherapy vs standard-of-care (SOC) perioperative chemotherapy alone in patients with newly diagnosed, advanced ovarian cancer.1

After an additional 7 months of monitoring, there was a 13-month improvement in median OS with the IMNN-001 regimen vs SOC regimen in intention-to-treat (ITT) population (HR, 0.69). Previously reported data from July 2024 showed that there was an 11.1-month improvement in OS for the experimental regimen vs SOC (HR, 0.74).2 The updated findings showed a total of 62% and 38% of patients in the IMNN-001 and SOC arms, respectively, survived more than 36 months from the beginning of study enrollment; more than 10% of patients have survived for 48 months or more.1 There was no change in the agent’s favorable safety profile.

Findings from OVATION 2 previously reported at the 2024 SITC Annual Meeting showed that at a median follow-up of 24 months, patients in the IMNN-001 arm (n = 58) experienced a median OS of 40.5 months (95% CI, 28.09-not evaluable) vs 29.4 months (95% CI, 24.94-45.60) in the SOC arm (n = 54; HR, 0.74; 95% CI, 0.42-1.30; P = .2963).3 Notably, the median OS in patients who received a PARP inhibitor regardless of exposure to IMNN-001 during treatment (n = 74) was not reached in the IMNN-001 arm vs 37.1 months in the SOC arm (HR, 0.41; 95% CI, 0.13-1.28).

IMNN-001 was also associated with an improvement in progression-free survival (PFS) in the ITT population, producing a median PFS of 14.9 months in the IMNN-001 arm vs 11.9 months in the control group (HR, 0.79; 95% CI, 0.51-1.23).

IMNN-001 is an interleukin 12 (IL-12) immunotherapy encapsulated in a nanoparticle delivery system.1 This design allows for cell transfection and subsequent persistent, local secretion of IL-12, a cytokine involved in the activation of anticancer immune responses.

“[Although] most research in ovarian cancer in recent years has focused on maintenance therapies for patients who have already responded to chemotherapy, the fact that we are seeing these positive results maintained in a population of newly diagnosed patients with advanced stages of disease requiring neoadjuvant chemotherapy is unprecedented and especially encouraging,” Premal Thaker, MD, MS, study chair of OVATION 2 and interim chief of Gynecologic Oncology, the David & Lynn Mutch Distinguished Professor of Obstetrics & Gynecology, and director of Gynecologic Oncology Clinical Research at Washington University School of Medicine in Saint Louis, Missouri, stated in a news release. “As the first immunotherapy to achieve clinically effective PFS and OS in ovarian cancer in conjunction with chemotherapy, we are especially excited to advance this promising program to a pivotal phase 3 clinical trial.”

OVATION 2 Trial Overview

The multicenter, open-label trial enrolled 112 patients at least 18 years of age with newly diagnosed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.4 Patients with high-grade serous adenocarcinoma, endometrioid adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, or adenocarcinoma not otherwise specified were also eligible. Notably, patients receiving hormonal therapy directed at the primary tumor were required to discontinue treatment at least 1 week prior to first study treatment.

Upon enrollment, patients were randomly assigned 1:1 to neoadjuvant and adjuvant chemotherapy plus 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 up to 17 doses; or chemotherapy alone. In both arms, the chemotherapy regimen comprised 175 mg/m2 of paclitaxel plus carboplatin at area under the curve 6 once every 3 weeks for 3 cycles as neoadjuvant therapy and another 3 cycles as adjuvant therapy.

The study’s primary end point was PFS. Key secondary end points included OS, objective response rate, chemotherapy response score, and surgical response.3,4 Notably, OVATION 2 was not powered for statistical significance.1

References

1. IMUNON announces continued strong improvement in overall survival data from randomized phase 2 OVATION 2 study of IMNN-001. IMUNON. December 10, 2024. Accessed December 10, 2024. https://investors.imunon.com/news-releases/news-release-details/imunon-announces-continued-strong-improvement-overall-survival
2. 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 December 10, 2024. https://investors.imunon.com/news-releases/news-release-details/imunon-announces-111-month-increase-overall-survival-patients
3. 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.
4. Study of IMNN-001 (also known as GEN-1) with NACT for treatment of ovarian cancer (OVATION 2). ClinicalTrials.gov. Updated November 26, 2024. Accessed December 10, 2024. https://clinicaltrials.gov/study/NCT03393884