Abstract KP03: NOVEL IMMUNOTHERAPEUTICS FOR OVARIAN CANCER

Abstract

Abstract In the last decade we have seen significance advances in the understanding of how the immune system modulates the ovarian tumor microenvironment and cancer growth. A number of studies have shown that high levels of tumor infiltrating adaptive immune system cells (B-cells and T-cells) found in ovarian cancer are associated with a favorable prognosis, especially if there is evidence of reduced regulatory T-cells. Robust T-cell tumor infiltration (TIL) is associated with PD-L1 upregulation. Almost half of ovarian cancers demonstrate enhanced PD-L1 expression on tumor cells and/or tumor infiltrating immune system cells. Immune checkpoint inhibitor monoclonal antibodies block receptors such as PD-1 and PD-L1 which suppress T-cell function. The largest study of immune checkpoint inhibition in ovarian cancer evaluated the blockade of PD-L1 using avelumab. In this phase I/II study 124 patients with recurrent disease, considered chemotherapy refractory, were treated with 10mg/kg avelumab every 2 weeks (65% of patients with 3 or greater salvage regimens). The overall response rate was 10% with a stable disease rate of 44% resulting in a disease control rate of 54%. Overall survival at 12 months was 44%. Clinical response did not correlate with either PDL-1 expression on tumor or immune infiltrating cells or BRCA mutation status. A randomized trial of avelumab in combination with pegylated liposomal doxorubicin in cisplatin refractory ovarian cancer has been initiated. Pre-clinical studies have shown that clinical responses to immune checkpoint inhibitor therapy in ovarian cancer may be enhanced by increasing Type I T-cell infiltration concurrent with therapy. Clinical strategies aimed at increasing TIL include the use of vaccines immunizing against ovarian cancer antigens to stimulate T-cells trafficking to tumor. Specific chemotherapy may result in increased TIL as some cytotoxic agents have been shown to modulate both the level and phenotype of TIL in ovarian cancer. An alternate approach is to suppress alternate pathways of tumor immune escape such as depletion of macrophage or inhibition of the IDO pathway to enhance immune activation. Several promising combination immunotherapy strategies are currently being evaluated in ovarian cancer. Citation Format: Mary L. Disis, MD. NOVEL IMMUNOTHERAPEUTICS FOR OVARIAN CANCER [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr KP03.