The phase 1/2 OVATION 2 study is expected to complete enrollment by the third quarter of this year.
Celsion’s GEN-1, an IL-12 DNA plasmid vector, was determined to have a satisfactory safety profile and acceptable risk/benefit by an independent Data Safety Monitoring Board (DSMB) that has recommended dosing to continue.1
Celsion, a clinical-stage company specializing in DNA-based immunotherapy and next-generation vaccines, made the announcement following a pre-planned interim safety review of patients treated in the multicenter phase 1/2 OVATION 2 study (NCT03393884). Based on the DSMB’s recommendation, the OVATION 2 study will continue to dose patients with 100 mg/m2 of GEN-1.
The DSMB analyzed safety data and concluded that weekly doses of GEN-1 in combination with standard neoadjuvant chemotherapy (NACT) were well-tolerated over a 6-month treatment course. There were no dose-limiting toxicities reported.
Interim efficacy data from the clinical trial has shown that the patients treated with GEN-1 in addition to NACT had improved rates of complete tumor resection compared with the patients in the control arm who only received treatment with NACT. The study primarily aims to achieve a 33% improvement in Progression Free Survival (PFS) in the GEN-1 treatment arm. Tumor regression is being categorized via Chemotherapy Response Score (CRS).
"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," Nicholas Borys, MD, Celsion's executive vice president and chief medical officer, said in a statement.1
All participants will undergo a NACT regimen consisting of paclitaxel 175 mg/m2 IV administered over 3 hours followed by carboplatin AUC 6 IV over 1 hour repeated every 3 weeks for 6 cycles. The patients in the experimental arm will additionally receive the 100 mg/m2 dose of GEN-1 on Days 8 and 15 of the first NACT cycle and then on Days 1, 8, and 15 of the subsequent 21-day NACT cycles for a total of 17 treatments.
The trial is open to female patients over the age of 18 who have a suspected histologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. Patients who have received prior treatment with GEN-1 or have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to GEN-1 will be excluded from the study. Analysis for PFS will be conducted after all patients have been followed for at least 16 months or a minimum of 80 events have been observed.
GEN-1 is developed with Celsion’s proprietary TheraPlas platform and is encased in a nanoparticle delivery system, which addresses toxicity issues typical of IL-12 administration. The therapy enables IL-12 delivery via cell transfection and local secretion at therapeutic levels.2 Toxicity is further reduced by targeted administration to the tumor location. In addition to ovarian cancer, studies have indicated potential for its use in treating colorectal and brain cancers.
"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),” Michael H. Tardugno, Celsion's chairman, president, and chief executive officer, added to the statement.1 “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."
Enrollment for the OVATION 2 study is expected to be completed by the third quarter of 2022, and PFS data are expected 12 months after patient enrollment is completed.