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

155 Background: This study evaluated weekly intraperitoneal GEN-1, an IL-12 plasmid formulated with polyethyleneglycol-polyethyleneimine cholesterol lipopolymer, in combination with dose-dense weekly taxane (T) and carboplatinum (C) every 3 weeks in newly diagnosed epithelial ovarian, fallopian tube, or primary peritoneal cancer (EOC) patients undergoing neoadjuvant therapy (NAC). The primary objective of this study was to evaluate the tolerability and safety of GEN-1 with NAC. Secondary objectives were objective clinical response and pathological complete response at interval debulking surgery (IDB). Methods: This protocol followed a standard 3+3 design. Patients received GEN-1 at escalating dose levels from 36 mg/m2, 47 mg/m2, 61 mg/m2, to 79 mg/m2 weekly for 8 treatments with concurrent T/C. After IDB, patients did not receive further GEN-1 but continued on T/C. Patients were assessed for dose limiting toxicities (DLT) and had tumor samples at a time of diagnostic laparoscopy and IDB. Translational endpoints are yet to be analyzed. Patients are being followed for every 3 months for 2 years. Results: Fifteen patients were enrolled and 9 patients received all 8 treatments with no DLTs. The 79 mg/m2GEN-1 cohort of patients are actively being treated. Two patients were screen failures; 1 patient discontinued prior to GEN-1 administration due to port site infection. Most common related toxicities were Gr 1 nausea, fatigue, abdominal pain, and vomiting. One patient experienced Gr 2 fevers associated with GEN-1 but responded to acetaminophen and fluids. One patient did not undergo IDB due to pulmonary embolism and severe deconditioning due to underlying cancer. Of the other 8 patients undergoing IDB: 3/8 had stable disease, 4/8 had partial responses (PR), and 1/8 had complete response (CR). There was 1 pathological CR, 3 micro PR, and 3 macro PR. All patients had a ≥ 89% drop in CA-125 following GEN-1. Conclusions: Adding GEN-1 to T/C is safe and appears to be active in NAC patients with newly diagnosed EOC. Updated results to be presented at meeting. Clinical trial information: NCT02480374.