A Phase 1/2 trial to evaluate the DNA-based immunotherapy GEN-1 in patients with newly-diagnosed advanced ovarian cancer has been cleared by the U.S. Food and Drug Administration (FDA) without restrictions, Celsion announced.
Recruitment for Phase 1 of the trial, called OVATION II (NCT03393884), is expected to begin by July this year and reach 25 percent of the enrollment goal of 90 patients by the end of 2018. The study will be conducted at up to 15 U.S. centers.
“GEN-1 holds the potential for tremendous promise as a cancer treatment in the rapidly emerging area of immunotherapy,” Michael H. Tardugno, Celsion’s chairman, president and chief executive officer, said in press release. “This new trial will evaluate GEN-1’s value as an adjuvant to current standard of care in newly diagnosed Stage III/IV ovarian cancer patients with a relatively healthy immune system.”
GEN-1 is a nanoparticle containing the DNA sequence for the pro-inflammatory protein interleukin-12 (IL-12). When delivered to a tumor site, GEN-1 induces a sustained production and release of IL-12, leading to an active immune response that kills tumor cells.
OVATION II is designed to evaluate the safety and effectiveness of GEN-1, and to shed light on its biological activity, in patients newly diagnosed with stage 3 or 4 epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.
“Designed in consultation with leading medical experts, this Phase I/II trial is expected to define an optimal dose, demonstrate GEN-1’s clinical benefit when compared with current standard of care, and provide insights on powering for a registration program as the candidate progresses through development,” Tardugno added.
The Phase 1 part of the trial is designed with a single dose escalation phase to 100 mg/m² to identify the best dose that is both safe and effective for inducing the maximum immune response.
In the Phase 2 part, the trial will continue at the selected dose in patients who are will be randomized to receive either GEN-1, injected directly into the peritoneum, plus standard of care chemotherapy — Paraplatin (carboplatin) and Taxol (paclitaxel) — or chemotherapy alone.
The study’s primary endpoint is to evaluate the therapy’s safety and assess progression free survival (PFS) — the time a a patient lives without disease progression — in both groups.
The Phase 1/2 trial was established after the positive results achieved by all patients in the Phase 1b OVATION trial (NCT02480374). Patients received escalating doses of GEN-1 (once a week for eight weeks) in combination with chemotherapy, followed by surgery.
Results showed that all patients had at least stable disease, and the majority (86 percent) experienced a decrease or complete elimination of their tumors after receiving GEN-1 plus chemotherapy.
A new analysis of the ongoing OVATION study has shown that among the 13 patients who received GEN-1, only four had cancer progression. In these four patients, PFS varied between 14 and 24.8 months, depending on the dose, which compares favorably to the median PFS of 12 months seen in patients with stage 3-4 ovarian cancer treated with standard chemotherapy plus surgery.
“In previous clinical studies performed to date, GEN-1 has demonstrated excellent safety and impressive clinical activity supported with dose-dependent, pro-immune improvement in the tumor micro environment. A one-time dose escalation may prove to be even more impressive,” said Dr. Nicholas Borys, Celsion’s senior vice president and chief medical officer.
“As we continue to follow patients, the latest PFS analysis from the OVATION study is showing a median of at least 15.4 months in the as-treated group, which compares favorably to a historical control of 12 months,” he said. “Our highest dose cohort has not demonstrated any progressions at our current 14-month follow up. This same cohort also had a 100% [complete] surgical resection rate.
“One of our patients in the OVATION study even had a complete pathological response,” Borys added.
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