OVATION 2 Study Reaches Full Enrollment for Advanced Ovarian Cancer

A phase 1/2 study of gene-mediated immunotherapy plus neoadjuvant chemotherapy completed its targeted enrollment of 110 patients with advanced ovarian cancer, according to a press release from Celsion Corporation.¹

The randomized, open-label, multicenter OVATION 2 trial (NCT03393884) is evaluating the dosing, safety, efficacy, and biological activity of the investigational agent GEN-1 in combination with neoadjuvant chemotherapy in patients with newly diagnosed stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer.

“We are delighted to reach this important milestone of completing enrollment in our phase 1/2 OVATION 2 study with GEN-1 and are optimistic the study will show our technology’s ability to deliver the powerful immune-modulating agent IL [interleukin]-12,” Corinne Le Goff, PhD, president and chief executive officer of Celsion Corporation, said in a statement.

GEN-1 is a DNA-mediated IL-12 immunotherapy that stimulates anticancer immune responses. GEN-1 contains a DNA plasmid in a synthetic polymer facilitating plasmid delivery vector to induce persistent local secretion of IL-12.

Patients in this trial are being randomly assigned to receive intravenous neoadjuvant chemotherapy using carboplatin and paclitaxel every 3 weeks for up to 6 cycles with or without 100 mg/m² of intraperitoneal GEN-1 on days 8 and 15 of the first cycle of chemotherapy, then on days 1, 8, and 15 of later cycles. Following the first 3 cycles of neoadjuvant chemotherapy, patients receive interval debulking surgery followed by 3 more cycles of chemotherapy.

The primary end point is progression-free survival (PFS), with the goal being a hazard ratio for progression or death of 0.75 favoring the GEN-1 arm at an 80% confidence interval, or a 33% improvement in PFS.

It was previously reported that a pre-planned interim safety review of 81 patients across both arms determined that safety was satisfactory with no dose-limited toxicities (DLTs) for patients who received 17 doses of GEN-1 over 6 months. The Data Safety Monitoring Board unanimously recommended continuing to treat patients with the 100 mg/m² dose of GEN-1 in this study.²

In terms of efficacy, it was reported in February 2022 that 39 patients had undergone interval surgery, leading to a 27% improvement in the rate of R0 resection—or margin-negative complete tumor resection with no gross or microscopic tumor remains in the tumor bed—in the GEN-1 arm. In June 2022, the company continued to state that the rate of R0 resection was improved in the GEN-1 arm and said that it also showed a higher rate of complete/near complete responses based on the chemotherapy response score.³ Results on PFS are expected to be reported approximately 12 months after full enrollment is reached.³

The previous phase 1 OVATION I trial (NCT02480374), which also treated patients with GEN-1 and neoadjuvant chemotherapy, determined the maximum tolerated dose of GEN-1 and showed no DLTs.⁴ Out of 14 evaluable patients, there were 2 radiological complete responses and 10 partial radiological responses prior to debulking, and 9 R0 patients and 1 complete pathological response at debulking. Common treatment-emergent adverse events included nausea, fatigue, abdominal cramping, anorexia, diarrhea, and vomiting. Grade 4 neutropenia was reported in 8 patients, but this was attributed to the chemotherapy.

GEN-1 received fast track designation from the FDA in February 2021.¹ Celsion stated that it plans to request FDA breakthrough therapy designation based on encouraging clinical data.

“Preliminary interim data in this study are very promising, showing both safety and activity,” said Le Goff. “We look forward to completing the study and reporting top line results in the second half of 2023.”

_References:

_{1. Celsion completes enrollment of the phase I/II OVATION 2 study with GEN-1 in advanced ovarian cancer. Celsion Corporation. September 15, 2022. Accessed September 20, 2022. https://bit.ly/3f8yIYJ}

_{2. Celsion reports data safety monitoring board unanimous recommendation to continue dosing patients in the phase II portion of the OVATION 2 study with GEN-1 in advanced ovarian cancer. Celsion Corporation. February 17, 2022. Accessed September 20, 2022. https://bit.ly/3LBedzR}

_{3. Celsion reports data safety monitoring board unanimous recommendation to continue dosing patients in the phase II portion of the OVATION 2 Study with GEN-1 in advanced ovarian cancer. Celsion Corporation. June 21, 2022. Accessed September 20, 2022. https://bit.ly/3dx6SVt}

_{4. Thaker PH, Bradley WH, Leath CA, et al. GEN-1 in combination with neoadjuvant chemotherapy for patients with advanced epithelial ovarian cancer:phase I dose-escalation study. Clin Cancer Res. 2021;27(20):5536-5545. doi:10.1158/1078-0432.CCR-21-0360}