Data Safety Monitoring Board Recommends Continued Dosing of GEN-1 for Advanced Ovarian Cancer in OVATION 2 Study

Investigators will continue treating patients with GEN-1 plus neoadjuvant chemotherapy following the results of a pre-planned interim safety review of the phase 1/2 OVATION 2 study.

A data safety monitoring board (DSMB) has unanimously agreed that the phase 1/2 OVATION 2 study (NCT03393884) should continue administering GEN-1 at a dose of 100mg/m2 for patients with advanced ovarian cancer following the results of a pre-planned interim safety review of 55 patients, according to a press release from drug developer Celsion Corporation.¹

Investigators reported that the trial, which had a confidence interval of 80%, identified a progression-free survival hazard ratio of 0.75, which translates to an approximate 33% improvement in risk of cancer progression in patients treated with GEN-1 and neoadjuvant chemotherapy vs neoadjuvant chemotherapy alone.

"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 at Celsion, said in a press release. "Continuing our clinical research program at the 100 mg/m2 dose in patients with advanced-stage ovarian cancer holds promise and is strongly encouraged by our study investigators and medical advisors."

The randomized, open-label, multicenter trial is evaluating the safety, dosing, and efficacy of IL-12 gene-mediated immunotherapy, GEN-1, in combination with standard-of-care neoadjuvant chemotherapy for patients with newly diagnosed stage III/IV ovarian cancer. Neoadjuvant chemotherapy is administered for 3 cycles to shrink the primary tumor prior to surgical resection. Patients then go on to receive interval debulking surgery as well as 3 subsequent cycles of chemotherapy to manage any residual tumor.

The immunotherapy agent GEN-1 had yielded tolerable and long-lasting levels of IL-12, which is a pluripotent cytokine associated with the stimulation of immune responses against cancer. The nanoparticle comprises a DNA plasmid–encoding IL-12 gene, as well as a synthetic polymer facilitating plasmid delivery vector. Notably, local and persistent IL-12 secretion at therapeutic levels follows cell transfection

Thus far, over half of the study's anticipated 110 patients have been enrolled on the trial. Interim data have indicated that of the first 36 patients who have undergone interval debulking surgery, 20 were given the experimental combination, 16 of whom (80%) have achieved a complete tumor resection (R0). This indicates a microscopically margin-negative resection. Moreover, of the patients who were treated with neoadjuvant chemotherapy only (n = 16), 56% had R0 resections. The objective response rate (ORR) by RECIST criteria were comparable between the 2 arms with both cohorts of patients achieving an ORR of approximately 80%.

Moreover, the DSMB reported that the combination has an acceptable risk/benefit, with patients tolerating up to 17 doses of GEN-1 in a course of treatment lasting up to 6 months with no dose-limiting toxicities.

GEN-1 was previously granted a fast track designation by the FDA in February 2021 for patients with advanced ovarian cancer.2 The indication was supported by findings from OVATION 2, the phase 1 portion of which yielded an R0 resection rate of 88% in the GEN-1 arm vs 50% in the neoadjuvant chemotherapy arm.

References

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 19, 2021. https://bit.ly/3Bh2jWn
Celsion Corporation receives FDA fast track designation for GEN-1 in advanced ovarian cancer. News release. Celsion Corporation. February 22, 2021. Accessed July 19, 2021. https://bit.ly/3BjDhFZ

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