A phase I trial of intraperitoneal EGEN-001, a novel IL-12 gene therapeutic, administered alone or in combination with chemotherapy in patients with recurrent ovarian cancer

Abstract

5572 Background: EGEN-001 (E1), an IL-12 expressing plasmid formulated with a novel gene delivery system, stimulates natural killer cells, IFN-γ secretion, and T-helper 1 response, inhibits tumor neovascularization, and has potent antitumor activity in preclinical models of ovarian cancer. The activity of E1 was evaluated in two early phase I clinical trials. Methods: Patients with recurrent ovarian cancer were treated intraperitoneally (IP) with escalating dosages and cycles of E1 alone or in combination with intravenous docetaxel and carboplatin. Study endpoints included the identification of clinical toxicity, the MTD, and antitumor activity. Results: In the initial phase 1A study, 13 patients were treated IP with 0.6–24 mg/m2 of E1. All patients except one in the 24 mg/m2 dose cohort completed all 4 weekly E1 treatments. The most commonly experienced adverse events included pyrexia (69%) and abdominal pain (54%). Three patients experienced peritonitis; one of these patients in the 24 mg/m2 cohort experienced a possibly reagent related DLT. The MTD was not identified. The overall clinical response was 31% stable disease and 69% progressive disease. Ten evaluable patients had measurable IL-12 plasmid DNA and IFN-γ levels in their peritoneal fluid. In the first cohort of patients enrolled in the phase 1B study, three patients have been treated with 12 mg/m2 of E1 IP every 10 days for 4 cycles in combination with docetaxel (75 mg/m2) and carboplatin (AUC 5) at 3 week intervals for a planned 6 cycles. All patients completed therapy. Two patients experienced mild pyrexia during E1 administration. One patient developed G3 anemia following the 4th cycle of E1 and required transfusion. No other G3/4 toxicities were noted. All patients demonstrated a partial response by CT evaluation and reductions in CA- 125 levels following the completion of E1 and two cycles of chemotherapy. Conclusions: IP administration novel IL-12 gene therapeutic E1 is feasable and demonstrates potential antitumor activity when given alone or in combination with chemotherapy in patients with recurrent ovarian cancer. Further development of E1 as a potential therapy for ovarian cancer is warranted. No significant financial relationships to disclose.