Adding GEN-1 to neoadjuvant chemotherapy (given before surgery to shrink tumors) increased the proportion of patients with complete removal of their tumors through surgery.
Its delivery system is made of nanoparticles designed to carry the DNA vector to cells at the tumor site. This would allow sustained production of IL-12 in the vicinity of the tumor, which is expected to improve the infiltration of immune cells and boost immune attacks against cancer.
IL-12 is one of the most active chemical messengers (cytokines) inducing anti-cancer immunity. However, its administration requires frequent injections and may lead to serious toxicity. GEN-1 was designed to circumvent these issues. Because it can be injected directly into the tumor site, it provides local increases in IL-12, with minimal effects on the rest of the body.
The safety and anti-tumor activity of GEN-1 has been demonstrated in animal models and in Phase 1 trials with advanced ovarian cancer patients. This includes the OVATION 1 study (NCT02480374), which studied GEN-1 in combination with standard neoadjuvant chemotherapy for newly-diagnosed ovarian cancer patients scheduled for surgery.
Building on encouraging results from this trial, Celsion launched the Phase 1/2 OVATION 2 study (NCT03393884) to further evaluate the safety, effectiveness and biological activity of GEN-1 plus chemotherapy for this group of patients.
Phase 1 of the study identified a GEN-1 dose considered safe and able to induce an optimal immune response (100 mg/m², injected into the abdominal cavity). In turn, Phase 2 will test whether this dose, combined to standard-of-care neoadjuvant chemotherapy (NACT; carboplatin and paclitaxel) is more effective than NACT alone.
Following therapy, patients in each group will undergo surgery to remove their tumors, followed by three additional cycles of chemotherapy.
The primary goal of OVATION 2 is to compare which regimen — GEN-1 plus NACT, or NACT alone — works best to extend the time until disease progression or death. Besides newly diagnosed advanced, or metastatic, ovarian (stage III/IV), the study also will assess treatment of fallopian tube or primary peritoneal cancer.
Fifteen patients already have been treated during Phase 1 — nine with GEN-1 (100 mg/m²) plus NACT, and six with NACT only.
Surgery was successful in all patients. However, while seven of the nine patients (78%) in the GEN-1 group had complete tumor removal after surgery (no cancer cells at the edge of the removed tissue), only three of six patients (50%) in the NACT-alone group had such clean removal.
Combining these results with data from OVATION 1, the 36 and 47 mg/m² doses of GEN-1 gave comparable results to higher doses (61, 79, 100 mg/m²), with both groups demonstrating about 80% objective response rate.
The trial’s first safety review showed no dose-limiting toxicities in any of the six evaluable patients — those who received at least four weekly doses of 100 mg/m² GEN-1. Injections into the abdomen of GEN-1 were well-tolerated, even when given with standard NACT.
“The clinical data at the three highest doses of GEN-1 showed an 82% R0 [complete] resection rate, compared with a 50% R0 resection rate for the NACT only control arm of the OVATION 2 study. Historical levels of R0 resections after interval debulking surgery range from 40% to 60%,” Nicholas Borys, MD, Celsion’s executive vice president and chief medical officer, said in a press release.
Michael H. Tardugno, Celsion’s chairman, president, and CEO added: “These data provide an early, but highly encouraging trend in both Phase I studies, and even more-so when the study populations are combined.”
“Confirmation that the 100 mg/m² dose is effective as a treatment for newly diagnosed ovarian cancer will be determined in the Phase 2 … which is expected to begin enrollment in the [second] half of 2020,” he said.
Information on contacts and locations, as well as updates on enrollment are available here. The trial is expected to recruit approximately 130 participants.
Celsion expects to share data from the last part of the study throughout 2021, with final data anticipated one year after full patient enrollment.