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Preliminary Results Of A Phase I/IIa Study Of BMS-986156 (glucocorticoid-induced Tumor Necrosis Factor Receptor–related Gene [GITR] Agonist), Alone And In Combination With Nivolumab In Pts With Advanced Solid Tumors.

Lillian L. Siu, Neeltje Steeghs, Tarek Meniawy, Markus Joerger, Jennifer L. Spratlin, Sylvie Rottey, Adnan Nagrial, Adam Cooper, Roland Meier, Xiaowei Guan, Penny Phillips, Gaurav Bajaj, Jochem Gokemeijer, Alan J. Korman, Kyaw Lwin Aung, Matteo S. Carlino

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104 Background: BMS-986156 is a fully human IgG1 agonist 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–programmed death-1 (PD-1). Here we describe preliminary dose escalation data from a phase I/IIa study of BMS-986156 ± nivolumab (anti–PD-1 mAb) in pts with advanced solid tumors (NCT02598960). Methods: During dose escalation, pts received BMS-986156 (10–800 mg) or BMS-986156 (30–800 mg) + nivolumab (240 mg) every 2 weeks. Objectives included safety (primary), immunogenicity, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy. Results: As of Dec 12, 2016, 66 pts were treated with BMS-986156 (n = 29) or BMS-986156 + nivolumab (n = 37).No dose-limiting toxicities (DLTs) were reported during dose escalation. The most common treatment-related adverse events reported with BMS-986156/BMS-986156 + nivolumab included pyrexia (21%/30%), chills (10%/16%), and fatigue (14%/14%); events were G1/2 in all pts except for 4 pts (6%) treated with the combination (G3 lipase [n = 1], G3 lung infection [n = 1], G3 fatigue [n = 1], and G3 aspartate aminotransferase with G4 creatine phosphokinase [n = 1; leading to discontinuation of treatment]). Preliminary data indicate that the incidence of immunogenicity to BMS-986156 was low when BMS-986156 ± nivolumab was administered. Preliminary data also indicate that BMS-986156 ± nivolumab exhibits linear PK with dose proportionality after a single dose, and BMS-986156 ± nivolumab is biologically active in PD analyses in peripheral blood. Initial antitumor activity has been observed in several pts treated with the combination; these data will be reported. Conclusions: This is the 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 BMS-986156 + nivolumab at doses predicted to be biologically active. Further evaluation of this combination in pts with advanced solid tumors is ongoing. Clinical trial information: NCT02598960.