Adding GEN-1 to Standard Chemotherapy Halts Advanced Ovarian Cancer Progression, Phase 1b Trial Shows

Adding GEN-1 to Standard Chemotherapy Halts Advanced Ovarian Cancer Progression, Phase 1b Trial Shows

A combination of Celsion’s DNA-based immunotherapy GEN-1 and standard chemotherapy halted disease progression in women with stage III/IV ovarian cancer eligible for surgery, according to results of a Phase 1b trial.

The findings also revealed that all patients on the highest GEN-1 dose had complete tumor removals, and approximately 86% of patients had a complete or partial response, meaning total or partial disappearance of cancer signs.

GEN-1 is a nanoparticle including the DNA sequence for the pro-inflammatory molecule interleukin-12 (IL-12). When delivered to the tumor, GEN-1 leads to a sustained production and release of IL-12, inducing an immune response against the tumor cells.

The OVATION I study (NCT02480374) in women with new stage III/IV ovarian cancer evaluated increasing doses of weekly GEN-1, for a total of eight doses, combined with three cycles of neoadjuvant chemotherapy — Paraplatin (carboplatin) and Taxol (paclitaxel) — before tumor-debulking surgery, which was followed by three more chemotherapy cycles.

GEN-1 doses started at 36 mg/m² and then increased to 47 mg/m², 61 mg/m², and 79 mg/m².

Results from the 13 patients who completed treatment showed a median progression-free survival (PFS) — the length of time patients live without cancer progression — of 24.3 months, which was higher in the higher-dose groups. When including the five patients who did not receive the full treatment course, PFS was 17.1 months.

“The OVATION I study results are highly encouraging,” Premal H. Thaker, MD, principal investigator in Celsion’s GEN-1 development program and a professor of gynecologic oncology at the Washington University School of Medicine in St. Louis, Missouri, said in a press release.

Thaker added that GEN-1 plus standard chemotherapy doubled PFS compared to historical data from women treated with chemotherapy alone, who show an average PFS of 12 months. “If the results from this early-stage study can be reproduced in a larger patient population, GEN-1 could represent a breakthrough treatment for newly diagnosed ovarian cancer patients.”

Treatment with GEN-1 was well-tolerated and no dose-limiting toxicities were found. Intraperitoneal (into the abdomen) administration of GEN-1 was feasible and had broad patient acceptance.

“We are very pleased with the results from the OVATION I trial,” said Nicholas Borys, Celsion’s senior vice president and chief medical officer, also noting the importance of early diagnosis and of the surgeon’s ability for removing tumors completely. “We hope this translates to an excellent long-term outcome for these women.”

Michael H. Tardugno, Celsion’s chairman, president, and CEO, said: “The observed clinical benefit in the OVATION I study is not only remarkable, it is supported with convincing translational data.”

Both Borys and Tardugno mentioned the recently started open-label, multi-center Phase 1/2 OVATION 2 study (NCT03393884), which will evaluate the safety, dosing, efficacy, and biological activity of a higher dose of GEN-1 in women with newly diagnosed, advanced, or metastatic ovarian, fallopian tube, or primary peritoneal cancer. OVATION 2 is still enrolling participants, Click here for more information.

The patients will be randomly assigned to either GEN-1 plus chemotherapy, or chemotherapy alone, prior to debulking surgery. Up to 130 patients will be included, approximately 12 in Phase 1 — intended to find a safe and effective dose of up to 100 mg/m² — and up to 118 in Phase 2.

The study’s main goal is to determine PFS, which will be determined after a minimum of 80 events (disease progression or death) or within at least 16 months of follow-up, whichever comes first.

“Our first data analysis from this open-label study is expected in the first half of 2019 and has the potential to be an important first proof point in determining the reproducibility of the OVATION I results,” Tardugno said.