FDA Backs Phase 3 Study of IMNN-001 in Advanced Ovarian Cancer
A phase 3 trial will evaluate IMNN-001, the first immunotherapy to show an overall survival benefit in ovarian cancer.
US FDA
- The FDA-aligned with a protocol to evaluate IMNN-001 with neoadjuvant chemotherapy (NACT) vs NACT alone, with overall survival (OS) as the primary end point.
- IMNN-001 previously demonstrated a 13-month median OS improvement (HR, 0.69) vs standard NACT in advanced ovarian cancer.
- Phase 2 data also showed enhanced tumor reduction, surgical resectability, and durable survival gains.
The FDA has aligned with the protocol for the pivotal phase 3 OVATION 3 trial of IMNN-001 for the treatment of patients with newly diagnosed advanced ovarian cancer.1
With this, the company is now initiating trial sites and working with investigators to begin enrolling patients in the study.
“We are grateful for the ongoing guidance and support from the FDA and are very pleased that the agency is fully aligned on our plans related to the phase 3 trial,” said Stacy Lindborg, PhD, president and chief executive officer of IMUNON, in a press release. “The phase 2 OVATION 2 study [NCT03393884] data are highly encouraging, demonstrating that IMNN-001 is the first immunotherapy to achieve a clinically effective response in ovarian cancer, including benefits in both progression-free and overall survival in frontline treatment, and we continue to observe strong improvements with additional monitoring and follow-up of patients.”
OVATION 3 plans to evaluate the safety and efficacy of IMNN-001 given at a dose of 100 mg/m2 intraperitoneally weekly plus NACT of paclitaxel and carboplatin vs standard of care (SOC) NACT alone. Patients are being randomly assigned in a 1:1 fashion.
Concept of gynecologic cancer: © tom - stock.adobe.com
The intent-to-treat population will include women with newly diagnosed advanced ovarian cancer who are eligible for neoadjuvant therapy. A subgroup of women who are positive for homologous recombination deficiency (HRD), including BRCA1 or BRCA2 mutations, will also be included. HRD-positive patients will receive poly ADP-ribose polymerase inhibitors as part of standard maintenance therapy.
The primary end point of the study is OS, and secondary end points are surgical response score, chemotherapy response score, clinical response and time to second-line treatment.
“We look forward to potentially replicating these unprecedented results in the phase 3 OVATION 3 study. We are currently initiating trial sites and are focused on enrolling study participants as quickly as possible as we work towards our goal of bringing thousands of women with advanced ovarian cancer a first-in-class and much-needed treatment option,” said Lindborg in the press release.
About the Prior OVATION 2 Trial
The OVATION 2 trialpreviously evaluated the dosing, safety, efficacy, and biological activity of IMNN-001 plus NACT of paclitaxel and carboplatin in patients newly diagnosed with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer.2 Patients with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma were eligible for enrollment in the study if they had adequate bone marrow, renal, hepatic, and neurologic function; an ECOG performance status of 0 to 2; and were free of active infection. Patients who received prior treatment with IMNN-001, currently were receiving treatment for active autoimmune disease, have other invasive malignancies, or have received prior radiotherapy or chemotherapy were not eligible for enrollment.
The open-label study randomized patients 1:1 to receive either paclitaxel/carboplatin plus IMNN-001 at a dose of 100 mg/m² weekly for up to 17 doses, or paclitaxel/carboplatin alone, followed by interval debulking surgery and adjuvant chemotherapy. The primary end point was progression-free survival, with secondary end points including objective response rate, chemotherapy response score, and surgical outcomes.
Although not powered for statistical significance, the study sought to explore whether combining IMNN-001 with NACT could enhance tumor reduction and surgical resectability compared to standard NACT alone.
Prior findings from the study were released in December 2024, showing that IMNN-001 plus NACT improved the median overall survival for patients with newly diagnosed, advanced ovarian cancer.3 After an additional 7 months of monitoring, a 13-month improvement in the median OS was seen with the IMNN-001 regimen vs SOC regimen ITT population (HR, 0.69). Prior data from July 2024 showed there to be an 11.1-month improvement in OS for the experimental regimen vs SOC (HR, 0.74).4
The updated findings from the study demonstrated a total of 62% and 38% of patients in the IMNN-001 and SOC arms survived more than 36 months from the beginning of study enrollment, respectively, and more than 10% of patients have survived for 48 months or more.3
References
IMUNON finalizes phase 3 study design with FDA for IMNN-001 in newly diagnosed advanced ovarian cancer. News release. IMUNON, Inc. March 24, 2025. Accessed March 25, 2025. https://tinyurl.com/mn4suw85
Study of IMNN-001 (also known as GEN-1) with NACT for treatment of ovarian cancer (OVATION 2). ClinicalTrials.gov. Updated January 28, 2025. Accessed March 25, 2025. https://clinicaltrials.gov/study/NCT03393884
IMUNON announces continued strong improvement in overall survival data from randomized phase 2 OVATION 2 study of IMNN-001. IMUNON. December 10, 2024. Accessed March 25, 2025. https://tinyurl.com/3wnf8crz
Imunon announces 11.1 month increase in overall survival in patients with newly diagnosed, advanced ovarian cancer treated with IMNN-001. News release. Imunon Inc. July 30, 2024. Accessed March 25, 2025. https://tinyurl.com/bdhtdm49
