Tolerance of Intraperitoneal (IP) Nivolumab After Extensive Debulking Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Patients With Advanced Ovarian Carcinoma

Summary

Spread pattern, the lack of alternative treatments, and emerging data on the activity of anti-Programmed death ligand 1 (PDL1) targeted checkpoint inhibitor therapy in gynecological cancers provide the rationale for this investigation. Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) are likely to increase the tumor-antigen expression and the mutational load. As a result, it would be interesting to combine this approach with immunotherapy. Moreover, Intraperitoneal (IP) infusion will directly target the peritoneal cavity and potentially enhance the immune response. Indeed some recent papers indicate that the peritoneum could be considered as a lymphoid organ, involving "milky spots", thus able to produce a better immune response when immunotherapy is given by IP route rather than intravenous (IV) route. The investigating team in Lyon, France is one of the major groups for HIPEC research in Europe (Pr O. Glehen et al) - Reference center for the tumors of the peritoneum (French National Cancer Institute). The aim of this study is to assess in this I/II phase study, the feasibility of extensive debulking surgery and HIPEC followed by Intraperitoneal (IP) nivolumab dose escalation in patients with advanced ovarian carcinoma.

Timeline

Start

2019-10-17

Primary completion

2022-10-03

Completion

2022-10-03

Outcome

Met primary endpoint

paper No dose-limiting toxicity was observed at any dose level in the 9 evaluable patients. PMID 38819408 ↗

paper This is the first study demonstrating the feasibility of IP nivolumab in patients with relapsed advanced ovarian cancer. PMID 38819408 ↗

Publications

• Corbaux P, Freyer G, Glehen O, You B, Bakrin N, Gelot A, Dayde D, Sajous C, Piffoux M, Peron J, Lescuyer G, Payen L, Kepenekian V. Intraperitoneal Nivolumab after Debulking Surgery and Hyperthermic Intraperitoneal Chemotherapy in Advanced Ovarian Cancer: A Phase I Study with Expansion Cohort. Clin Cancer Res. 2024 Aug 15;30(16):3438-3446. doi: 10.1158/1078-0432.CCR-24-0507.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Nivolumab	Monoclonal antibody	0.3 mg/kg	Other
Subject	Nivolumab	Monoclonal antibody	0.5 mg/kg	Other
Subject	Nivolumab	Monoclonal antibody	1 mg/kg	Other
Subject	Nivolumab	Monoclonal antibody	3 mg/kg	Other

Indications