Immunotherapy GEN-1 Demonstrates Acceptable Risk/Benefit Profile in Advanced Ovarian Cancer

The novel gene-mediated immunotherapy GEN-1 showcased satisfactory safety with an acceptable risk/benefit profile when given over a 6-month period with up to 17 doses in newly diagnosed patients with stage III/IV ovarian cancer, according to interim data from the phase 1/2 OVATION 2 study (NCT033393884).¹

As such, the Data Safety Monitoring Board (DSMB) for the trial has unanimously recommended that the study continue to treat participants with GEN-1 at a dose of 100 mg/m².

To date, more than half of the projected 110 participants have been enrolled to the trial. Of the first 36 patients who have undergone interval debulking surgery on the study, 20 received treatment with GEN-1 at a dose of 100 mg/m² plus neoadjuvant chemotherapy. Of those who were given the immunotherapy, 80% had a complete tumor resection (R0). A total of 16 patients received neoadjuvant chemotherapy alone, and 56% of these patients had R0 resections.

Additionally, the objective response rates, per RECIST criteria, proved to be comparable between the patients who received neoadjuvant chemotherapy alone and those who received GEN-1 at a dose of 100 mg/m², with both cohorts achieving a rate of 80%.

“We thank the DSMB members for their work and advice,” Michael H. Tardugno, chairmain, president, and chief executive officer of Celsion Corporation, stated in a press release. “We are encouraged by the current rate of patient recruitment and expect to complete enrollment around the end of this year.”

In the phase 2 trial, investigators examined GEN-1 plus standard-of-care neoadjuvant chemotherapy in this population. After NACT, patients underwent interval debulking surgery, which was then followed by 3 adjuvant cycles of chemotherapy and up to 9 additional weekly treatments of GEN-1. The trial was 80% powered to demonstrate the equivalent of a 33% improvement in progression-free survival (HR, 0.75), which served as the primary end point vs the control arm.

Patients needed to have a suspected histologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, to participate. Moreover, they needed to have a FIGO of III or IV; adequate bone marrow, renal, hepatic, and neurologic function; and an ECOG performance status of 0 to 2.²

Those who had prior GEN-1, a history of allergic reactions attributed to compounds of similar chemical or biologic composition to GEN-1, prior oral or parenteral corticosteroids within 2 weeks of study entry, or those receiving treatment for active autoimmune disease were excluded.

Study participants who were randomized to the investigative arm received intravenous paclitaxel at a dose of 175 mg/m², which was followed with carboplatin at area under the curve of 6 on day 1; this was repeated every 3 weeks for 6 treatment cycles. GEN-1 was delivered at a dose of 100 mg/m² on days 8 and 15 of the first cycle of neoadjuvant chemotherapy; the agent was then administered on days 1, 8, and 15 of the subsequent 21-day cycles of neoadjuvant chemotherapy for a total of 17 treatments. Patients in the control arm received the same neoadjuvant chemotherapy regimen as the investigative arm.

When investigators analyzed the phase 2 results in combination with the surgical resection rates reported in the prior phase 1b OVATION 1 study, which had the same inclusion criteria as the phase 1/2 trial, the data proved to reflect the robust dose-dependent efficacy of adding GEN-1 to neoadjuvant chemotherapy.

Among 22 patients who had received 0 mg/m², 36 mg/m², or 47 mg/m² of GEN-1 in combination with neoadjuvant chemotherapy, 50% had R0 resections. Among 28 patients who received GEN-1 at higher doses of 61 mg/m², 79 mg/m², or 100 mg/m², 82% achieved R0 resections.

“These findings show a consistent dose-dependent clinical response in both surgical outcome and tumor response, which is further supported by translational data of the tumor microenvironment,” Nicholas Borys, MD, executive vice president and chief medical officer of Celsion, added in the release. “Continuing our clinical research program at the 100 mg/m² dose in patients with advanced ovarian cancer holds promise and is strongly encouraged by our study investigators and medical advisors.”

Additional data from the phase 1 trial showed that all patients in the high-dose cohorts experienced a complete response (CR) or partial response (PR) to treatment.³ However, 67% of those in the lower-dose cohorts also reported a CR or PR with the immunotherapy.

Moreover, when investigators compared matched patient data in a synthetic control arm from the trial, patients who received GEN-1 were found to experience a doubling in disease control vs the control arm. However, the data did not achieve statistical significance because of the small number of patients that were included in the analysis.

In February 2021, the FDA granted a fast track designation to GEN-1 for use as a potential therapeutic option in patients with advanced ovarian cancer.

References

1. Celsion reports Data Safety Monitoring Board recommendation to continue dosing patients in the phase II portion of the OVATION 2 study with GEN-1 in advanced ovarian cancer. News release. Celsion Corporation. July 19, 2021. Accessed July 20, 2021. https://bit.ly/3zgJh0j
2. Study of GEN-1 with NACT for treatment of ovarian cancer (OVATION 2) (OVATION 2). ClinicalTrials.gov. Updated June 28, 2021. Accessed July 20, 2021. https://clinicaltrials.gov/ct2/show/NCT03393884
3. Celsion Corporation receives FDA fast track designation for GEN-1 in advanced ovarian cancer. News release. Celsion Corporation. February 22, 2021. Accessed July 20, 2021, 2021. http://bit.ly/3dBCpTE