On February 25, 2021 Celsion Corporation (NASDAQ: CLSN), a clinical-stage development company focused on DNA-based immunotherapy and next-generation vaccines, reported an update on its Phase I/II OVATION 2 Study with GEN-1 in patients with advanced ovarian cancer, including interim observations (Press release, Celsion, FEB 25, 2021, View Source [SID1234575744]). GEN-1 is Celsion’s DNA-mediated interleukin-12 (IL-12) immunotherapy designed using TheraPlas, its proprietary, synthetic, non-viral nanoparticle delivery system platform.

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The OVATION 2 Study combines GEN-1 with standard-of-care neoadjuvant chemotherapy (NACT) in patients newly diagnosed with Stage III/IV ovarian cancer. NACT is designed to shrink the cancer as much as possible for optimal surgical removal after three cycles of chemotherapy. Following NACT, patients undergo interval debulking surgery, followed by three adjuvant cycles of chemotherapy and up to nine additional weekly GEN-1 treatments, the goal of which is to delay progression and improve overall survival. The OVATION 2 Study is an open-label, 1-to-1 randomized trial, 80% powered to show the equivalent of a 33% improvement in progression-free survival (PFS) (HR=0.75), the primary endpoint, when comparing the treatment arm (standard of care + GEN-1) with the control arm (standard of care alone).

To date, the Company has enrolled approximately one-third, or 34 patients, of the anticipated 110 patients to be enrolled into the OVATION 2 Study, of which 20 are in the treatment arm and 14 are in the control. Currently, 27 patients have had their interval debulking surgery with the following results:

12 of 15, or 80%, of patients treated with GEN-1 had a R0 resection, which indicates a microscopically margin-negative complete resection in which no gross or microscopic tumor remains in the tumor bed.
7 of 12 patients, or 58%, of patients in the control arm had an R0 resection.
This interim data represents a 38% improvement in R0 resection rates for GEN-1- patients compared with control arm patients and is consistent with the reported improvement in resection scores noted in the encouraging Phase I OVATION I Study, the manuscript of which has been submitted for peer review publication.
"As the goal for surgical debulking is to eliminate microscopic disease, more ovarian cancer patients require neoadjuvant chemotherapy. However, little progress has been made in adding additional efficacious immunotherapy agents to standard neoadjuvant chemotherapy," said Premal H. Thaker, M.D., MSc., Professor in Gynecologic Oncology and Director of Gynecologic Oncology Clinical Research at Washington University School of Medicine in St. Louis and lead Principal Investigator for the OVATION 2 Study. "The results seen to date in the OVATION 2 Study are exciting and impactful for ovarian cancer patients."

The Company further reports that 22 clinical sites in the U.S. and Canada have been initiated, with three more sites expected to be added by the end of the first quarter. Clinical investigators met in early February in a virtual meeting and expressed excitement about the potential for GEN-1 to treat advanced ovarian cancer and, despite the challenges and earlier delays posed by the COVID-19 pandemic, they remain committed to completing enrollment in the study during the second half of 2021.

Commenting on the interim patient reports, Dr. Nick Borys, chief medical officer of Celsion, said, "We are gratified that such a high proportion of GEN-1 patients had no residual disease at the time of their debulking surgery. These results are consistent with what we observed in our Phase I (OVATION I) study. This is great news for the patients and the surgeons in our study as a R0 resection suggests a good clinical outcome. We are following our patients carefully to see how well they do long term. The OVATION 2 investigators remain enthusiastic about the potential of GEN-1 to treat late-stage ovarian cancer, which currently has few treatment options."

Celsion announced earlier this week that GEN-1 had received Fast Track designation from the U.S. Food and Drug Administration (FDA). This designation is intended to facilitate the development and expedite the regulatory review of drugs to treat serious conditions and fill an unmet medical need. According to the FDA, a Fast Track Drug must show some advantage over available therapy, including:

Showing superior effectiveness, effect on serious outcomes or improved effect on serious outcomes
Avoiding serious side effects of an available therapy
Decreasing a clinically significant toxicity of an available therapy that is common and causes discontinuation of treatment
About GEN-1 Immunotherapy

GEN-1, designed using Celsion’s proprietary TheraPlas platform technology, is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system, which 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 anti-cancer immunity acting through the induction of T-lymphocyte and natural killer (NK) cell proliferation. The Company has previously reported positive safety and encouraging Phase I results with GEN-1 given as monotherapy or a combination therapy in patients with advanced peritoneally metastasized primary or recurrent ovarian cancer, and recently completed a Phase Ib dose-escalation trial (OVATION 1 Study) of GEN-1 in combination with carboplatin and paclitaxel in patients with newly diagnosed ovarian cancer.