Phase 1 study of intraperitoneal infusion of autologous monocytes with peginterferon alfa-2b and interferon gamma-1b in women with recurrent or refractory ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.

TPS3092 Background: Monocytes can differentiate into classic M1 macrophages inhibiting tumor proliferation and promoting natural killer (NK) cell differentiation. We previously demonstrated that the combination of human monocytes, human interferon alfa-2b (IFNα-2b), and interferon gamma-1b (IFNγ 1b) act synergistically against tumor cells in vitro and in mouse models, providing a long and durable response. Additionally, monocytes, IFNα and IFNγ have been individually shown in early phase clinical trials to be safely administered intraperitoneally. As ovarian cancer is largely confined to the peritoneal cavity, it is likely that the administration of IFNs and monocytes intraperitoneally will create a strong anti-tumor environment and can overcome the immunosuppressive environment of epithelial ovarian cancer. We hypothesize that the monocyte and interferon administration will be tolerable to women with relapsed ovarian cancer. Methods: A Phase 1 single arm study to determine the maximum tolerated dose of intraperitoneal monocytes and pegylated IFNα-2b and IFNγ-1b is currently enrolling patients with recurrent or refractory ovarian cancer, fallopian tube cancer or primary peritoneal cancer without standard therapy options. Autologous monocytes obtained through apheresis 24 hours prior will be mixed with pegylated IFNα-2b and IFNγ-1b in a 3 + 3 dose escalation and administered intraperitoneally once every 28 days. Results: As of February 2017 we are enrolling our first cohort of patients and are evaluating for dose limiting toxicities. Conclusions: This is a novel therapy that if successful, may be efficacious alone or used to create a backbone on which to add novel agents such as SMAC mimetics or PD-L1 blockade, in order to increase immune-mediated killing of ovarian cancer. Clinical trial information: NCT 02948426.