GEN-1 is a nanoparticle containing the DNA sequence for the pro-inflammatory protein interleukin-12 (IL-12). When delivered to the tumor, GEN-1 induces a sustained production and release of IL-12, triggering an immune response against the tumor cells.
“We are very excited to advance our ovarian cancer research, the foundation of which is based on a known anti-cancer agent, IL-12. Over the past three decades, IL-12 has convincingly demonstrated its capability to actively recruit the body’s immune system to work against cancers. However, its clinical promise has been limited by a poor safety profile. GEN-1 has the potential to address this,” Michael H. Tardugno, Celsion’s chairman, president and chief executive office, said in a press release.
“In our novel, gene-mediated formulation, we believe GEN-1 has the potential to effectively harness IL-12’s antitumor activity for cancer patients with a dimension of safety not found in the free, recombinant form,” he added.
The OVATION II study (NCT03393884), approved by the U.S. Food and Drug Administration in January 2018, will evaluate the safety and efficacy of GEN-1 in patients with newly diagnosed advanced or metastatic ovarian, fallopian tube, or primary peritoneal cancer.
Phase 1 of the trial will include 12 patients to identify a dose that is both safe and induces the best immune response. Patients will receive doses of up to 100 mg/m².
After selecting the appropriate dose, Phase 2 of the study will randomize 118 patients to receive GEN-1 plus standard of care chemotherapy — Paraplatin (carboplatin) and Taxol (paclitaxel) — or chemotherapy alone. GEN-1 will be injected directly into the peritoneum.
Patients in the GEN-1 treatment group will receive the therapy before and after surgery to reduce the tumor’s mass.
The study’s primary objective is to assess whether adding GEN-1 to standard chemotherapy extends the time until disease progression or death compared to chemotherapy alone. Researchers expect to observe a 33 percent improvement.
Researchers will conduct their analysis after at least 80 events (disease progression or death) have been observed or within at least 16 months of followup, whichever is first.
“OVATION II is designed to define the optimal dose of GEN-1 and provide important insights into GEN-1’s clinical benefit as an adjuvant therapy both before and after debulking surgery with the potential to stimulate an anticancer immune response, compared to the current standard of care alone,” Tardugno said.
The Phase 1/2 trial was established after the positive results achieved in the OVATION Phase 1b trial (NCT02480374). All 13 patients who received GEN-1 (doses up to 79 mg/m2) achieved at least stable disease, and 86 percent saw a partial or complete resolution of their tumors.
A more recent analysis showed that four patients eventually showed signs of cancer progression, but it was 14 to 24.8 months before that happened.
“The overall median progression-free survival (PFS) in the first OVATION study recently reached 24 months among patients treated per protocol. These data compare favorably to the historical median PFS of 12 months for newly diagnosed patients with Stage III and IV ovarian cancer who undergo neoadjuvant chemotherapy followed by interval debulking surgery,” said Nicholas Borys, Celsion’s senior vice president and chief medical officer.
Final data from OVATION is expected by the end of 2018, he said.
“In previous studies, GEN-1 was shown to be well-tolerated at doses up to 79 mg/m2 with meaningful, dose-dependent, pro-immune clinical activity,” Borys said. “GEN-1’s safety profile and evident dose response have led us to initiate this new trial at a higher dose of 100 mg/m2.
“We believe that GEN-1 dosing before and after debulking surgery in combination with neoadjuvant chemotherapy will maximize the therapeutic effect of GEN-1.”