FDA Grants Fast Track Status to Immunotherapy GEN-1 in Advanced Ovarian Cancer

February 22, 2021 - The FDA has granted a fast track designation to the DNA-mediated interleukin-12 immunotherapy GEN-1 for use in the treatment of patients with advanced ovarian cancer.



The FDA has granted a fast track designation to the DNA-mediated interleukin-12 (IL-12) immunotherapy GEN-1 for use in the treatment of patients with advanced ovarian cancer, according to an announcement from Celsion Corporation.1

Previously, findings from the phase 1 portion of the phase 1/2 OVATION 2 trial (NCT033393884) showed that 88% of patients with newly diagnosed, stage III/IV ovarian cancer (n = 7/8) who received GEN-1 plus neoadjuvant chemotherapy (NACT) experienced a complete tumor resection (R0), indicative of microscopically margin-negative resection in which no gross or microscopic tumor remained in the tumor bed. Patients who received NACT only achieved a R0 resection rate of 50%.

“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,” Michael H. Tardugno, chairman, president, and chief executive officer of Celsion, stated in a press release. “We are optimistic that GEN-1 represents a game-changer for women with advanced ovarian cancer who have limited treatment options.”

Developed using Celsion’s exclusive TheraPlas platform technology, GEN-1 is an IL-12 DNA plasmid vector that is enclosed in a nanoparticle delivery system that permits cell transformation followed by persistent, local emission of the IL-12 protein. Importantly, IL-12 is an active cytokine that is involved in the initiation of strong anticancer immunity that acts through the induction of T-lymphocyte and natural killer cell production.

In the open-label phase 2 trial, investigators evaluated GEN-1 with standard-of-care NACT in this patient population. Following NACT, patients underwent interval debulking surgery; this is followed by 3 adjuvant cycles of chemotherapy and up to 9 additional weekly GEN-1 treatments. The trial was 80% powered to show the equivalent of a 33% improvement in progression-free survival (PFS; HR, 0.75), which was the primary end point versus the control arm.

To be eligible for enrollment, patients had to have suspected histologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal carcinoma; a FIGO of III or IV; acceptable bone marrow, renal, hepatic, and neurologic function; and an ECOG performance status of 0, 1, or 2.2

If they had had previously received GEN-1, had a history of allergic reactions attributed to compounds of similar chemical or biologic composition to GEN-1, if they had received oral or parenteral corticosteroids within 2 weeks of study entry, or if they were receiving treatment for active autoimmune disease, they could not participate.

Those who were randomized to the investigative arm received intravenous (IV) paclitaxel at 175 mg/m2, followed by carboplatin at area under the curve of 6 on day 1; this was repeated every 3 weeks for 6 treatment cycles. GEN-1 was given at a dose of 100 mg/m2 on days 8 and 15 of the first cycle of NACT and then on days 1, 8, and 15 of the subsequent 21-day NACT cycles for a total of 17 treatments. In the control arm, patients received the same NACT regimen as the experimental arm.

Data from the phase 1b dose-escalation OVATION I trial demonstrated encouraging objective response rates with the GEN-1/NACT combination. All patients in the high-dose cohorts achieved a complete response (CR) or partial response (PR) to treatment. Moreover, 67% of patients in the lower-dose cohorts also reported a CR or PR with GEN-1. The rates of R0 resection were 88% versus 33% in high- and low-dose cohorts, respectively.

When comparing matched patient data in a synthetic control arm with data from OVATION I, patients who received GEN-1 experienced a doubling in terms of disease control versus the synthetic control arm; however, these findings do not have statistical significance because of the small number of patients included.

In the intent-to-treat population (n= 15) the hazard ratio (HR) for PFS with GEN-1/NACT was 0.53 (95% CI, 0.16-1.73; log-rank, P = .29). The HR in the per-protocol population (n = 14) was 0.33 (95% CI, 0.08-1.37; log-rank, P = .11).


  1. Celsion Corporation receives FDA fast track designation for GEN-1 in advanced ovarian cancer. News release. Celsion Corporation. February 22, 2021. Accessed February 22, 2021. http://bit.ly/3dBCpTE
  2. Study of GEN-1 with NACT for treatment of ovarian cancer (OVATION 2) (OVATION 2). ClinicalTrials.gov. Updated February 1, 2021. Accessed February 22, 2021. https://clinicaltrials.gov/ct2/show/NCT03393884
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