Phase I study of the safety and activity of formulated IL-12 plasmid administered intraperitoneally in combination with neoadjuvant chemotherapy in patients with newly diagnosed advanced stage ovarian cancer.

Abstract

5568 Background: This study evaluated weekly intraperitoneal (IP) GEN-1, an IL-12 plasmid formulated with polyethyleneglycol-polyethyleneimine cholesterol lipopolymer, with intravenous (IV) weekly taxane (T) and carboplatinum (C) every 3 weeks in epithelial ovarian, fallopian tube or primary peritoneal cancer (EOC) patients undergoing neoadjuvant therapy (NAC). The primary objective was to evaluate the tolerability and safety of GEN-1 with NAC. Secondary objectives included objective clinical response and pathological response at interval debulking surgery (IDB). Methods: Newly diagnosed advanced stage EOC patients being treated with NAC were eligible. The trial utilized a 3+3 design with GEN-1 IP dose levels of 36 mg/m2, 47 mg/m2, 61 mg/m2, and 79 mg/m2 weekly for 8 treatments with concurrent IV T/C. Dose-limiting toxicity (DLT) was based on the first 4 doses of GEN-1 administered. Results: To date, 13 patients have been treated on-study with 12 patients receiving all 8 treatments of IP GEN-1 with no DLTs. The most common related toxicities were Gr 1 nausea, vomiting, abdominal pain and fatigue. One patient experienced Gr 2 fevers associated with GEN-1 but responded to acetaminophen and fluids. One patient did not undergo IDB while on-study due to a cancer related pulmonary embolism and severe deconditioning. This patient has since improved and will have IDB. Conclusions: Adding GEN-1 to neoadjuvant T/C is safe and appears to be active in EOC patients. We are reporting the interim findings; final results with translational data to be presented. Clinical trial information: NCT02480374. [Table: see text]