Celsion Corporation, the immunotherapy’s developer, expects to enroll up to 118 patients in this second part of the study by the end of 2021, and will provide clinical updates throughout the course of treatment.
“We are delighted to have begun enrolling patients in the Study and look to achieve our goal of providing new novel therapeutic options to patients with this difficult-to-treat cancer,” Michael H. Tardugno, chairman, president, and CEO of Celsion, said in a press release.
GEN-1 consists of a DNA vector coding for the pro-inflammatory protein interleukin (IL)-12, one of the most active chemical messengers (cytokines) inducing anti-cancer immunity. However, IL-12 needs to be administered frequently by injection, which may lead to serious toxicity.
The investigational treatment was designed to circumvent these issues. It is delivered to the tumor site by nanoparticles designed to carry the DNA vector, thereby promoting a sustained production of IL-12 in the vicinity of the tumor, while having minimal effects on the rest of the body. This is expected to boost an immune attack against cancer cells by aiding the infiltration of immune cells into the tumor.
The Phase 1/2 OVATION 2 study (NCT03393884) will evaluate the safety, effectiveness, and biological activity of adding GEN-1 to neoadjuvant chemotherapy (given before surgery to shrink tumors) in patients with newly diagnosed advanced or metastatic (stage 3/4) ovarian, fallopian tube, or primary peritoneal cancer.
In the Phase 1 part of the study, researchers identified a GEN-1 dose considered safe and able to induce an optimal immune response (100 mg/m², injected into the abdominal cavity).
Then patients in each group will undergo surgery to remove their tumors, followed by three additional cycles of chemotherapy.
The trial’s main (primary) goal is to assess which of the two regimens — GEN-1 plus NACT, or NACT alone — can extend the time until disease progression. Researchers expect to observe a 33% improvement with GEN-1.
Early data from Phase 1 showed that adding GEN-1 to neoadjuvant chemotherapy increased the proportion of patients whose tumors were found to be completely removed through surgery.
Surgery was successful in all 15 patients enrolled in this part of the trial. However, while seven of the nine patients (78%) treated with GEN-1 had complete tumor removal after surgery (no cancer cells at the edge of the removed tissue), this was seen in three of six patients (50%) in the NACT-alone group.
“Based on results from earlier studies, we believe this regimen holds great potential to alter the current treatment paradigm, and in doing so improve survival for ovarian cancer patients, whose prognosis is generally poor,” said Tardugno.
Preclinical and clinical data, including that of the OVATION 1 study (NCT02480374), have also confirmed the safety and anti-tumor activity of GEN-1 plus standard neoadjuvant chemotherapy for newly-diagnosed advanced ovarian cancer.
In the OVATION 1 study, adding GEN-1 to standard chemotherapy stopped disease progression in this patient population and helped with complete tumor removal during surgery.
Further evaluation suggested that adding GEN-1 to standard chemotherapy nearly doubled the time until disease progression or death, although it didn’t reach statistical significance due to the small number of patients.
“These findings are not statistically significant … but nonetheless are encouraging and supportive of our current Phase II study,” said Nicholas Borys, MD, Celsion’s chief medical officer.
The therapy previously received an orphan designation from the U.S. Food and Drug Administration for the treatment of ovarian cancer.