614P Tolerance and preliminary efficacy of intraperitoneal (IP) nivolumab after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients (pts) with advanced ovarian carcinoma: A phase I study with expansion cohort (ICONIC)

Abstract

Cytoreductive surgery and HIPEC combination with IP immunotherapy is likely to have a synergistic effect, through an increase of tumor-antigen expression and mutational load. We aimed to determine the safety of IP nivolumab after CRS and HIPEC in heavily-pretreated pts with recurrent ovarian carcinoma (NCT03959761). In this monocentre study, pts were treated according to 3 dose-levels of IP nivolumab following a 3+3 design (0.5, 1.0 and 3.0 mg/kg), starting 5 to 7 days after CRS and HIPEC, and repeated every 2 weeks for 4 infusions through an IP catheter. The primary objective was to demonstrate the feasibility of IP nivolumab based on dose limiting toxicity (DLT) at each dose-level. Secondary objectives were to assess changes over time in disease progression and changes in tolerance of CRS, HIPEC and post procedure intravenous chemotherapy. A total of 9/10 pts enrolled into the dose escalation cohort were evaluable for DLT (1 IP catheter disconnection after the 2nd IP infusion). No DLTs have been observed at either dose-level according to an independent data safety monitoring board (DSMB). Therefore, 7 pts were included into an expansion cohort with 3.0 mg/kg IP nivolumab. Overall, six pts (35.3%) did not complete all planned cycles, 4 pts due to IP catheter complications (2 painful injections, 1 disconnection, 1 infection) and 2 pts due to early tumor progression. No deaths due to treatment occurred. Nine pts (52.9%) experienced severe adverse events (SAEs), including 4 related to IP catheter. SAEs were transaminases elevation (6 pts, grade 3-4, related to CRS), hemodynamic shock (1 pt, related to CRS), hypokalemia (1 pt, related to CRS and HIPEC), portal vein thrombosis (1 pt, related to CRS). There were no SAEs related to IP nivolumab and no immune related adverse events, except 1 pt with lowering TSH levels. With a median follow-up of 10.1 months (95%CI 8.2-NA), median progression-free-survival was 7.4 months (95%CI 6.0-NA). IP nivolumab was feasible and well tolerated, warranting further investigations at 3 mg/kg with other immunotherapy combinations.