Expert Discusses Celsion’s Ovarian Cancer Immunotherapy GEN-1; Phase 1/2 Trial Still Enrolling

The ovarian cancer immunotherapy candidate GEN-1, which is being tested in a Phase 1/2 clinical trial in newly diagnosed patients with advanced disease, was the focus of a recent call with a gynecologic oncology expert.

The OVATION 2 trial (NCT03393884) is enrolling at 34 sites across the U.S. It will test the safety and effectiveness of GEN-1 in up to 130 patients with newly diagnosed advanced or metastatic ovarian (stage III/IV), fallopian tube, or primary peritoneal cancer.

GEN-1, developed by Celsion Corporation, is a nanoparticle containing a vector with the DNA sequence for the pro-inflammatory protein interleukin (IL)-12. Delivery to the tumor cells is followed by release of IL-12, which induces anti-cancer immune responses by activating immune T-cells and natural killer (NK) cell proliferation.

The call about ovarian cancer treatments and emerging opportunities was led by Premal H. Thaker, MD, a scientist key in the development of GEN-1, and was hosted by the investment bank Oppenheimer & Co. All slides from the presentation may be viewed here. Other potential treatments for patients with ovarian cancer were discussed.

Thaker is study chair and a member of the Data Safety Monitoring Board for OVATION 2, and was a principal investigator for the OVATION 1 Phase 1b study (NCT02480374), which studied GEN-1 in combination with standard chemotherapy for newly-diagnosed ovarian cancer patients scheduled for surgery.

OVATION 1 results showed that all 14 patients who received the two higher GEN-1 doses (61 mg/m² and 79 mg/m²), along with chemotherapy, responded at least partially to treatment, while 88% had complete tumor removal after surgery.

In contrast, partial or complete cancer disappearance was seen in only 60% of those on the two lower doses (36 mg/m² and 47 mg/m²), Thaker noted in a press release.

The patients who completed the eight weekly treatments were free from cancer progression for 21 months, which dropped to 17.1 months among the participants who failed to complete all treatment sessions.

Now, the Phase 1 of OVATION 2 seeks to identify a GEN-1 dose — up to 100 mg/m² and injected into the peritoneum — that is both safe and induces an optimal immune response in advanced ovarian cancer patients.

Phase 2 of the study will test the dose selected in the first part along standard chemotherapy — Paraplatin (carboplatin) and Taxol (paclitaxel) — or chemotherapy alone, to compare if add-on GEN-1 extends the time until disease progression or death.

Thaker, who is a professor of obstetrics and gynecology in the division of gynecologic oncology at Washington University School of Medicine in St. Louis, Missouri, stated that levels of key ovarian cancer biomarkers revealed a marked reduction in immunosuppressive response after treatment. That indicates “GEN-1 may alter the tumor microenvironment and may improve ovarian cancer outcomes” when combined with chemotherapy, she said.

“I was encouraged by this promising data,” she said. “As Study Chair of the OVATION 2 study,” Thaker added, “I am eager to see if these results can be duplicated in a larger patient population.”

Michael Tardugno, Celsion’s chairman, president and CEO, said the company aims to provide an effective treatment to women with ovarian cancer. Results of the first part of OVATION 2 are expected in the second half of 2019, he said.

According to Celsion, preclinical and clinical data suggest that GEN-1 also may be effective in the treatment of colorectal and brain cancers.