Celsion has released the latest update from the its OVATION Phase 1b clinical trial (NCT02480374), showing that combining GEN-1 with standard of care for newly diagnosed advanced ovarian cancer patients induces superior progression-free survival (PFS) rates compared to historical controls.
The study is enrolling women with newly diagnosed stage III and IV ovarian cancer to receive Celsion’s innovative immunotherapy, GEN-1 – an interleukin (IL)-12 vector that is formulated into nanoparticles and is administered in combination with neoadjuvant chemotherapy, followed by interval debulking surgery. The gene is transferred into tumor cells so that it enhances innate and adaptive immune responses.
Out of five patients enrolled in the first two cohorts, only in one patient has the cancer progressed after 11.7 months. The remaining four patients in these two cohorts have now an average PFS of 15.1 months. One patient has been progression-free for 19.1 months. None of the patients in the third or fourth dosing cohorts have shown any signs of disease progression to date.
This is compares favorably to the median PFS of 12 months seen in newly diagnosed women with advanced disease who undergo neoadjuvant chemotherapy followed by secondary surgery (also known as interval debulking surgery), which is performed after two to four cycles of neoadjuvant chemotherapy.
“This new data on progression-free survival adds to the impressive clinical findings seen across a number of meaningful measures used to assess ovarian cancer, like a 75 percent objective tumor response rate and a greater than 50 percent R0 (margin-negative) surgical resection rate,” Dr. Nicholas Borys, Celsion’s chief medical officer, said in a press release. “The consistency and robust nature of the data across all four cohorts and the encouraging clinical responses underscore the potential of GEN-1 to serve as an effective, safe IL-12 immunotherapy in ovarian cancer.”
Celsion’s has also reported preliminary translational research findings from the first four patient cohorts. Patients treated with escalating doses of GEN-1 (36 mg/m², 47 mg/m², 61 mg/m², 72 mg/m²) combined with standard neoadjuvant chemotherapy showed a successful transfer of the IL-12 gene, increasing in a dose-dependent manner. The IL-12 uptake also translated into immune system activity and significant increases in IFN-gamma. These signs were evident already at 24 hours after injecting GEN-1 and chemotherapy.
Analysis of tumor tissue from several patients, collected before treatment and after completing eight weeks of GEN-1 treatments, showed a significant increase of infiltrating immune cells. It also showed a clear reversal from an immunosuppressive status to a pro-inflammatory environment after treatment with GEN-1.
“These translational research findings demonstrate that GEN-1 in ovarian cancer patients is biologically active and creates an immuno-stimulatory cytokine milieu in the peritoneal cavity in a dose-dependent manner and promotes a pro-immune T-cell population dynamics in the tumor micro-environment,” said Dr. Khursheed Anwer, Celsion’s executive vice president and chief science officer.