FDA Grants Fast Track Designation to GEN-1 for Advanced Ovarian Cancer

A novel DNA-mediated interleukin-12 (IL-12) immunotherapy, GEN-1, had been granted a Fast Track designation by the FDA for the treatment of advanced ovarian cancer, according to a press release from the Celsion Corporation.¹

“Fast Track designation is an important step in developing GEN-1 for advanced ovarian cancer. Presuming the encouraging data we are generating in early clinical studies continues, this designation supports an expedited path to market,” said Michael H. Tardugno, chairman, president, and CEO, Celsion., in a statement.

GEN-1 is currently under investigation in the phase 2 portion of the OVATION 2 study (NCT03393884), in which the agent is being investigated in combination with neoadjuvant chemotherapy as treatment of patients with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. The trial was initiated in June 2020 after positive results were observed in the phase 1b portion of the study.^2,3

In the phase 1b portion, a cohort of 15 patients with advanced ovarian cancer were enrolled. Nine patients were treated with GEN-1 at 100 mg/m² plus neoadjuvant chemotherapy and compared with 6 patients who received neoadjuvant chemotherapy alone.³

All patients in the study achieved an objective response to GEN-1 in the high-dose cohorts and 67% achieved objective responses in the low-dose cohorts. Although not statistically significant, the GEN-1 plus neoadjuvant chemotherapy arm had a longer progression-free survival (PFS) compared with those who received neoadjuvant chemotherapy alone (HR, 0.53; 95% CI, 0.16-1.73; log-rank P = .29).

The goal behind treating patients with the combination was to prepare them for interval debulking surgery followed by 2 cycles of chemotherapy. The full cohort of patients were able to undergo resection and 78% of those who received GEN-1 in combination with neoadjuvant chemotherapy had R0 resection. In comparison, only 50% of the neoadjuvant chemotherapy arm had an R0 resection. These results for GEN-1 represent strong dose-dependent efficacy

when compared with the prior phase 1b data. The R0 resection rates observed were 42% among patients who received GEN-1 at a dose level of 0, 36, or 47 mg/m2 plus neoadjuvant chemotherapy, and 82% for those who received 61, 79, or 100 mg/m2 of GEN-1 in combination with neoadjuvant chemotherapy.

No dose-limiting toxicities were observed with GEN-1 in the phase 1/2 OVATION 2 study at the highest dose level of 100 mg/m2 and after 4 weekly doses. Overall., intraperitoneal administration of GEN-1 plus neoadjuvant chemotherapy was well-tolerated in the study patients.

In the open-label, randomized OVATION 2 study, a total of 130 patients will be enrolled and randomized to either GEN-1 plus neoadjuvant chemotherapy or neoadjuvant chemotherapy alone. According to the study protocol, it is 80% powered to show the equivalent of a 33% improvement in PFS, which is the primary end point of the study.¹

To be eligible for the study, patients must have histologically diagnosed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma along with histological documentation of the original primary tumor. Patients are also required to have an International Federation of Gynecology and Obstetrics stage of III or IV; an ECOG performance status of 0 to 2; and adequate bone marrow, hepatic, renal, and neurological function.

_References:

_{1. Celsion Corporation receives FDA Fast Track Designation for GEN-1 in advanced ovarian cancer. News release. Celsion Corporation. February 22, 2021. Accessed February 23, 2021. https://bit.ly/3ke5ohT}

_{2. Celsion Corporation initiates phase II OVATION 2 study of GEN-1 in advanced ovarian cancer. News release. Celsion Corporation. July 27, 2020. Accessed February 23, 2021. https://bit.ly/3ujDntI}

_{3. Celsion Announces highly encouraging initial clinical results from the phase i portion of the phase I/II OVATION 2 study with GEN-1 in patients with advanced ovarian cancer. News release. Celsion Corporation. March 19, 2020. Accessed February 23, 2021. https://bit.ly/2ZOR8T3}