Intraperitoneal Nivolumab After Debulking Surgery and Hyperthermic Intraperitoneal Chemotherapy in Advanced Ovarian Cancer: A Phase I Study with Expansion Cohort.

ABSTRACT

PURPOSE: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are expected to be synergistic with intraperitoneal (IP) immunotherapy by increasing tumor antigen expression and mutational load. We assessed the feasibility and safety of IP nivolumab following complete CRS and HIPEC in pretreated patients with recurrent ovarian cancer (ClinicalTrials.gov identifier NCT03959761). PATIENTS AND METHODS: Patients received IP nivolumab (0.5, 1 and 3 mg/kg) using a 3+3 dose-escalation design, starting 5-7 days after CRS and HIPEC. Four IP Q2W nivolumab infusions were planned. The primary objective was to demonstrate the feasibility of IP nivolumab based on dose-limiting toxicity (DLT). Secondary objectives were to assess changes in tolerance of CRS and HIPEC. RESULTS: A total of 17 patients were enrolled including 10 patients in the dose-escalation and 7 patients in the expansion phase. No DLT was observed at any dose-level in the 9 evaluable patients. Six of the 17 patients (35%) did not complete all planned infusions 4 (23.5%) due to peritoneal catheter complications, 2 (11.8%) due to early progression. No procedure-related deaths occurred. Eleven patients (65%) experienced serious adverse events (SAEs), mainly transitory grade 3-4 transaminases elevations (6/11), and surgery-related (9/11). Four SAEs were related to the peritoneal catheter and two to HIPEC. No SAEs/grade 3-4 adverse events related to IP nivolumab occurred. CONCLUSIONS: This is the first study demonstrating the feasibility of IP nivolumab in patients with relapsed advanced ovarian cancer; further investigation at 3 mg/kg is warranted.