PD-1 signal inhibitors for ovarian cancer: Perspectives and issues

Abstract

Several clinical trials of PD-1/PD-L1 signal-blockade agents (PD-1 inhibitors: anti-PD- 1 or -PD-L1 antibodies) have exhibited dramatic antitumor efficacy in patients with certain types of solid malignancies. Based on our clinical studies of cancer immune escape in ovarian cancer, we conducted the first principal investigator initiated, Phase II clinical trial of anti-PD-1 antibody, nivolumab in 20 patients with platinumresistant recurrent ovarian cancer. Among all 20 patients, response rate (RR) was 15%. Median overall survival was 20.0 months, respectively (Hamanishi et al. JCO 2015). In our ongoing follow-up study subsequent to this trial, two patients with a CR have each survived without any disease progression for over one year, with no adjuvant antitumor treatment. Besides, two other clinical trials with another anti-PD-1 antibody (pemblorizumab) and anti-PD-L1 antibody (avelumab) have been reported. Additionally, several trials of the combination with first line or second line chemotherapies, molecular targeted drugs or other immune-check inhibitors such as anti-CTLA-4 antibodies have recently begun. The exploration of predictive biomarkers related to antitumor response of anti-PD-1 inhibitors has started by using not only immunohistochemistry but also genome-wide analyses of tumor tissues or immune cells in the world. We also conducted comprehensive gene expression analysis and next generation sequencing of both T cell and B cell receptor (T/B cell repertoire assay) from blood sampling of the patients in our clinical trial. In this session, we will highlight several recent clinical trials using PD-1 inhibitors and discuss the clinical perspectives and issues including our exploration of predictive biomarkers by genome-wide analyses in ovarian cancer.