Peripheral and tumor immune correlates in patients with advanced melanoma treated with combination nivolumab (anti-PD-1, BMS-936558, ONO-4538) and ipilimumab.

3003^ Background: Nivolumab and ipilimumab are fully human monoclonal antibodies that block the immune checkpoint receptors PD-1 and CTLA-4, respectively. In a multi-cohort, phase I study of nivolumab/ipilimumab combination therapy in melanoma patients (pts), objective response rates up to 47% were observed (NCT01024231). Putative predictive biomarkers from peripheral blood (PB) or tumor, including tumor PD-L1 expression, absolute lymphocyte count (ALC) and PB myeloid derived suppressor cells (MDSC) were evaluated. Pharmacodynamic changes in activated and effector T cells were also assessed. Methods: Tumor PD-L1 membrane expression was assessed in archival FFPE specimens by immunohistochemistry (28-8 PD-L1 antibody). ALC was measured in serial PB samples; changes in the percentage, number and phenotype of activated CD4+ and CD8+T cells and MDSC were characterized by flow cytometry. Results: PD-L1 expression was seen in 37% (10/27) of pts, using a cut-off of 5% tumor cell membrane staining. Objective respo...