GEN-1 immunotherapy demonstrated dose-dependent efficacy results in newly diagnosed patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer when treated in combination with the standard of care, according to results from the OVATION 2 study. Based on positive data in the phase I portion, the study is moving on to phase II with enrollment expected to begin in the second half of the year.
GEN-1 immunotherapy demonstrated dose-dependent efficacy results in newly diagnosed patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (EOC) when treated in combination with the standard of care, according to results from the OVATION 2 Study, Celsion announced in a press release.1Based on positive data in the phase I portion, the study is moving on to phase II with enrollment expected to begin in the second half of the year.1
Overall there were 15 patients included in the study, 9 of which were treated with immunotherapy and neoadjuvant chemotherapy and 6 of whom received neoadjuvant chemotherapy alone. Surgical resection rates, another efficacy outcome, were satisfactory in this study. All 15 patients had successful resections of their tumors. Seventy-eight percent of patients in the GEN-1 arm had a complete surgical resection (R0), while only 50% of patients who received neoadjuvant chemotherapy alone had an R0.
Data from phase I were combined with results from a prior phase Ib trial and showed robust dose-dependent efficacy with the addition of GEN-1 to neoadjuvant chemotherapy.
The objective response rate was approximately 80% both in patients treated at lower doses and in patients treated with higher doses of GEN-1.
"The combined data from our previous phase Ib dose-escalating trial (OVATION 1 Study) plus this latest data from the phase I portion of the OVATION 2 Study further confirms the encouraging dose-dependent efficacy of GEN-1 plus NACT. The clinical data at the 3 highest doses of GEN-1 showed an 82% R0 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, executive vice president and chief medical officer of Celsion, said in a statement.
An independent Data Safety Monitoring Board also reviewed the initial safety data from the first 15 patients in the study and found that there were no dose-limiting toxicities in the 6 evaluable patients who received at least 4 weekly doses of GEN-1 at 100 mg/m2.
Results from the phase Ib OVATION 1 Study presented at the 2019 ASCO-SITC Clinical-Oncology Symposium by Premal H. Thaker, MD, suggested that GEN-1 plus neoadjuvant chemotherapy is active in patients newly diagnosed with EOC.2
The efficacy analysis was positive for response to treatment across 4 dosages, which included 2 complete responses (CRs) and 10 partial responses (PRs). Two patients also had stable disease. In terms of debulking status, 9 patients had an R0, 3 patients had an R1, and 2 patients had an R2. Pathologic responses were observed in 14 patients total. Of these, 1 was a complete pathologic response, 6 were micro pathologic responses, and 7 were macro pathologic responses.
OVATION 2 is an ongoing open-label, multicenter, randomized study that aims to enroll 130 participants to evaluate the safety, dosing, efficacy, and biological activity of intraperitoneal GEN-1 plus neoadjuvant chemotherapy compared with neoadjuvant chemotherapy only.1
In the immunotherapy arm, patients receive the interleukin (IL)-12 plasmid formulated with PEG-PEI-cholesterol lipopolymer plus carboplatin area under the curve (AUC) 6 intravenously (IV) and paclitaxel 175 mg/m2IV, both on day 1 of each cycle. Patients in the neoadjuvant chemotherapy arm receive equivalent doses of carboplatin and paclitaxel.
The study is 80% powered to demonstrate the equivalent of a 33% improvement in progression-free survival, the primary end point of the study, with the addition of GEN-1 to neoadjuvant chemotherapy.
To enroll in the study, patients are required to have a histologic diagnosis of EOC with histologic documentation of the original primary tumor. Patients are also required to have an International Federation of Gynecology and Obstetrics (FIGO) of III or IV; adequate bone marrow, renal, hepatic, and neurologic function; and an ECOG performance status of 0 to 2.
GEN-1 is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system. It has 4 distinct mechanisms of action, which are the activation and proliferation of natural killer cells, maturation and proliferation of T cells, and enhancing the innate and adaptive immunity of IL-12 cells. GEN-1 has previously shown signals of promise in other gynecologic cancers as well.2