On July 30, 2024 IMUNON, Inc. (NASDAQ: IMNN), a clinical-stage company in late-stage development with its DNA-mediated immunotherapy, reported positive topline results from the Phase 2 OVATION 2 Study with IMNN-001 in patients with advanced ovarian cancer (Press release, IMUNON, JUL 30, 2024, View Source [SID1234645156]). OVATION 2 is a randomized study of IMNN-001 in combination with neoadjuvant and adjuvant chemotherapy (NACT) inclusive of interval debulking or cytoreductive surgery compared with a control arm of standard-of-care NACT alone. IMNN-001 is the Company’s interleukin-12 (IL-12) immunotherapy based on its TheraPlas technology.

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Highlights from patients treated with IMNN-001 plus standard-of-care in a first-line treatment setting include:

An 11.1 month increase in median OS compared with standard-of-care alone in the intent-to-treat population (ITT).
A hazard ratio in the ITT population of 0.74, which indicates a 35% improvement in survival.
Among the approximately 90% of trial participants who received at least 20% of specified treatments per-protocol in both study arms, patients in the IMNN-001 arm had a 15.7 month increase in median OS, representing a further extension of life with a hazard ratio of 0.64, a 56% improvement in survival.
For the nearly 40% of trial participants treated with a poly ADP-ribose polymerase (PARP) inhibitor, the hazard ratio decreased further to 0.41, with median OS in the IMNN-001 treatment arm not yet reached at the time of database lock, compared with median OS of 37.1 months in the standard-of-care treatment arm.
The PFS results, the trial’s primary endpoint, support the OS results with:

A three-month improvement in PFS compared with standard-of-care alone.
A hazard ratio in the intent-to-treat population of 0.79, indicating a 27% improvement in delaying progression for the IMNN-001 treatment arm.
"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," said Stacy Lindborg, Ph.D., President and Chief Executive Officer of IMUNON. "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."

OVATION 2 evaluated the dosing, safety, efficacy and biological activity of intraperitoneal administration of IMNN-001 in combination with NACT of paclitaxel and carboplatin in patients newly diagnosed with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer. Treatment in the neoadjuvant period is designed to shrink the tumors as much as possible for optimal surgical removal after three cycles of chemotherapy. Following NACT, patients undergo interval debulking surgery, followed by three additional cycles of adjuvant chemotherapy to treat any residual tumor. This open-label study enrolled 112 patients who were randomized 1:1 and evaluated for safety and efficacy to compare NACT plus IMNN-001 versus standard-of-care NACT. In accordance with the study protocol, patients randomized to the IMNN-001 treatment arm could receive up to 17 weekly doses of 100 mg/m2 in addition to NACT.

As a Phase 2 study, OVATION 2 was not powered for statistical significance. Additional endpoints included objective response rate, chemotherapy response score and surgical response.

Sebastien Hazard, M.D., Chief Medical Officer of IMUNON, added, "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 progression-free survival and in the patients who received three doses or more of IMNN-001 gaining an additional 15.7 months of life, while the safety profile was tolerable. It suggests that IMUNON’s IL-12 gene therapy has a long-term impact on the disease."

Commenting on the study results, Premal H. Thaker, M.D, Interim Chief of Gynecologic Oncology, David & Lynn Mutch Distinguished Professor of Obstetrics & Gynecology, Director of Gynecologic Oncology Clinical Research at Washington University School of Medicine, and the OVATION 2 Study Chair, said, "Typically an increase in survival of six months is considered to be clinically meaningful, and extending survival from 29 months with standard-of-care treatment to 40 months with the addition of IMNN-001 is compelling. Importantly, the extension of survival among IMNN-001 patients also exposed to the new standard that includes PARP inhibitors is even greater. If confirmed in a Phase 3 clinical trial, IMNN-001 could reset the standard of care for women with ovarian cancer."

Charles A. "Trey" Leath, III, M.D., Director, Division of Gynecologic Oncology, Ellen Gregg Shook Culverhouse Chair in Gynecologic Oncology, Professor, Department of Obstetrics and Gynecology at University of Alabama Medical Center, and OVATION 2 Principal Investigator, said, "I (We) have been investigating IMNN-001 since the Phase 1 OVATION 1 Study and continue to be frustrated by the lack of substantial progress in primary treatment options available to treat this disease. The results from this trial demonstrating that IMNN-001 could extend life by one year or longer are provocative and powerful. I believe that should efficacy be confirmed in a pivotal study, IMNN-001 will be quickly incorporated into the care regimen."

IMUNON plans to hold an End-of-Phase 2 meeting with the U.S. Food and Drug Administration as soon as possible to discuss the protocol for a Phase 3 study, which is anticipated to begin in the first quarter of 2025. IMUNON also plans to present full OVATION 2 Study results at an upcoming medical conference and to submit the results for publication in a peer-reviewed medical journal.

Conference Call and Webcast

IMUNON is hosting a conference call at 8:30 a.m. Eastern time today to discuss OVATION 2 Study results, next steps and to answer questions. Dr. Thaker will be joining management on the call. To participate in the conference call, please dial 833-816-1132 (Toll-Free/North America) or 412-317-0711 (International/Toll) and ask for the IMUNON call. A live webcast of the call will be available here.

Participants are encouraged to preregister for the call here.

The call will be archived for replay through August 13, 2024. The replay can be accessed at 877-344-7529 (U.S. Toll-Free), 855-669-9658 (Canada Toll-Free) or 412-317-0088 (International Toll), using the replay access code 7783601. A webcast of the call will be available here for 90 days.

About IMNN-001 Immunotherapy

Designed using IMUNON’s proprietary TheraPlas platform technology, IMNN-001 is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system that enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anticancer immunity acting through the induction of T-lymphocyte and natural killer cell proliferation. IMUNON previously reported positive safety and encouraging Phase 1 results with IMNN-001 administered as monotherapy or as combination therapy in patients with advanced peritoneally metastasized primary or recurrent ovarian cancer, and completed a Phase 1b dose-escalation trial (the OVATION 1 Study) of IMNN-001 in combination with carboplatin and paclitaxel in patients with newly diagnosed ovarian cancer.

About Epithelial Ovarian Cancer

Epithelial ovarian cancer is the sixth deadliest malignancy among women in the U.S. There are approximately 20,000 new cases of ovarian cancer every year and approximately 70% are diagnosed in advanced Stage III/IV. Epithelial ovarian cancer is characterized by dissemination of tumor in the peritoneal cavity with a high risk of recurrence (75%, Stage III/IV) after surgery and chemotherapy. Since the five-year survival rates of patients with Stage III/IV disease at diagnosis are poor (41% and 20%, respectively), there remains a need for a therapy that not only reduces the recurrence rate, but also improves overall survival. The peritoneal cavity of advanced ovarian cancer patients contains the primary tumor environment and is an attractive target for a regional approach to immune modulation.