BMS-986156 is a fully human IgG1 agonist monoclonal antibody (mAb) that binds GITR and promotes T effector–cell activation and possible reduction/inactivation of T regulatory cells. Preclinical data show enhanced antitumor T-cell activity with anti-GITR + anti–PD-1. Here we describe preliminary dose-escalation data from a phase 1/2a study of BMS-986156 ± nivolumab (anti–PD-1 mAb) in patients with advanced solid tumors (NCT02598960).
During dose escalation, patients received BMS-986156 (10–800 mg) or BMS-986156 (30–800 mg) + nivolumab (240 mg) every 2 weeks. Objectives included safety (primary), immunogenicity, pharmacokinetics, pharmacodynamics, and antitumor activity.
As of March 31, 2017, 66 patients were treated with BMS-986156 monotherapy (n=29) or BMS-986156 + nivolumab (n=37). No dose-limiting toxicities (DLTs) were reported during dose escalation. The most common treatment-related AEs with BMS-986156/BMS-986156 + nivolumab included pyrexia (21%/32%), chills (10%/19%), and fatigue (10%/16%); events were grade 1/2 in all patients except 6 patients (9%) treated with the combination (G3 increased lipase [n=1], G3 lung infection [n=1], G3 dehydration [n=1], G3 fatigue [n=1], G3 colitis [n=1; led to treatment discontinuation], and G3 increased hepatic enzyme with G4 increased creatine phosphokinase [n=1; led to treatment discontinuation]). Preliminary data with BMS-986156 ± nivolumab indicate low immunogenicity to BMS-986156, linear pharmacokinetics with dose proportionality after a single dose, and biologic activity in pharmacodynamic analyses in peripheral blood. Initial antitumor activity was observed with the combination, including responses in patients who progressed on/after prior anti–PD-1 therapy; these data will be reported.
In this first report of clinical data with an anti-GITR mAb ± a PD-1 inhibitor, BMS-986156 ± nivolumab was well tolerated, with no DLTs and low immunogenicity. Antitumor activity was observed with the combination at doses predicted to be biologically active. Further evaluation of this combination in patients with advanced solid tumors is ongoing.