On June 21, 2022 Celsion Corporation (NASDAQ: CLSN), a clinical-stage company focused on DNA-based immunotherapy and next-generation vaccines, reported that following a pre-planned interim safety review of 87 as treated patients (46 patients in the experimental arm and 41 patients in the control arm) randomized in the Phase I/II OVATION 2 Study with GEN-1 in advanced (Stage III/IV) ovarian cancer, the Data Safety Monitoring Board (DSMB) has unanimously recommended that the OVATION 2 Study continue treating patients with the dose of 100 mg/m2 (Press release, Celsion, JUN 21, 2022, View Source [SID1234616112]). The DSMB also determined that safety is satisfactory with an acceptable risk/benefit, and that weekly doses of GEN-1 were well tolerated during a course of treatment that is given over six months in combination with standard neoadjuvant chemotherapy. No dose-limiting toxicities were reported.

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The OVATION 2 Study combines GEN-1, the Company’s IL-12 gene-mediated immunotherapy, 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 additional cycles of chemotherapy to treat any residual tumor.

The OVATION 2 Study is designed with an 80% confidence interval to show an approximate 33% improvement in risk for cancer progression, Progression Free Survival, when comparing the treatment arm (NACT + GEN-1) with the control arm (NACT only). GEN-1 is an immunotherapy that produces safe and durable local levels of IL-12, a pluripotent cytokine associated with the stimulation of innate and adaptive immune response against cancer. The GEN-1 nanoparticle comprises a DNA plasmid encoding IL-12 gene and a synthetic polymer facilitating plasmid delivery vector. Cell transfection is followed by persistent, local secretion of the IL-12 protein at therapeutic levels.

The Company also announced that more than 87% of the projected 110 patients have been enrolled in the OVATION 2 Study. Interim clinical data from patients who have undergone interval debulking surgery showed that the GEN-1 treatment arm is showing improvement in R0 surgical resection rates and CRS 3 chemotherapy response scores over the control arm. A complete tumor resection (R0) is a microscopically margin-negative resection in which no gross or microscopic tumor remains in the tumor bed. The chemotherapy response score is a three-tier standardized scoring system for histological tumor regression into complete/near complete (CRS 3), partial (CRS 2) and no/minimal (CRS 1) response based on omental examination.

"Findings from our OVATION 2 study show a consistent favorable trend in both surgical outcome and tumor response, which is further supported by translational data of the tumor microenvironment," noted Nicholas Borys, M.D., Celsion’s executive vice president and chief medical officer. "We are encouraged by the current rate of patient recruitment and expect to complete enrollment by the third quarter of 2022. The primary endpoint for the study is progression-free survival (PFS) which we expect to report approximately 12 months after patient enrollment is completed."

In February 2021, the Company announced that GEN-1 received FDA Fast Track Designation in advanced ovarian cancer. Celsion plans to request FDA Breakthrough Therapy Designation for GEN-1 based on the encouraging clinical data.

"We again want to thank the DSMB members for their work and advice," said Michael H. Tardugno, Celsion’s chairman, president and chief executive officer. "Preclinical and clinical data gives us every reason to believe in GEN-1’s promise for ovarian cancer patients along with the support from leading medical researchers of the Gynecological Oncology Group (GOG). FDA Fast Track Designation for GEN-1 in advanced ovarian cancer coupled with the GOG’s interest in forging a partnership to develop GEN-1 in ovarian cancer will assist Celsion in its plans for an accelerated registrational program."

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 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.

About Epithelial Ovarian Cancer

Epithelial ovarian cancer (EOC) is the fifth deadliest malignancy among women in the United States. There are approximately 22,000 new cases of ovarian cancer every year and the majority (approximately 70%) are diagnosed in advanced stages III and IV. EOC is characterized by dissemination of tumor in the peritoneal cavity with a high risk of recurrence (75%, stage III and IV) after surgery and chemotherapy. Since the five-year survival rates of patients with stages III and 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 regional approach to immune modulation.