Biomarker characterization using mass cytometry in a phase 1 trial of urelumab (BMS-663513) in subjects with advanced solid tumors and relapsed/refractory B-cell non-Hodgkin lymphoma.

3017 Background: Anti-CD137 antibody was shown in both murine cancer models and in a first-in-human, phase I trial (Sznol et al., 2008) to increase peripheral activated CD8 T cells and IFN-inducible genes, thereby facilitating a cytolytic, antitumor, Th1 response. A multiparametric immune pharmacodynamic assessment of the effects of anti-CD137 therapy has not been previously performed. Methods: We employed the novel technology of mass cytometry time of flight (CyTOF) to investigate the patient’s global immune status prior to and during a phase 1 study (NCT01471210) of Urelumab, a fully human anti-CD137 antibody, administered once per 3-week cycle in patients with solid tumors and B-cell non-Hodgkin’s lymphoma. Peripheral blood was obtained at 4 time points throughout treatment (baseline, 24-hrs after 1st dose of cycle 1, immediately before cycle 2, and post cycle 3 at response evaluation, C3R). PBMCs were isolated and stimulated for 4 hours with PMA/ionomycin. Immune cell characterization and function wer...