INCAGN02385 is an antagonist antibody targeting the co-inhibitory receptor LAG-3 for the treatment of human malignancies

Lymphocyte activation gene 3 (LAG-3) is a cell surface receptor that negatively regulates antigen-specific T cell responses. LAG-3 expression is generally restricted to populations of recently activated and chronically stimulated exhausted T cells, and is often correlated with general T cell dysfunction across several human malignancies. Accordingly, the LAG-3 pathway has been identified as a potential barrier to productive tumor-specific T cell immunity generated by PD-1/PD-L1 blockade. The antitumor activity from targeting the LAG-3 pathway in preclinical models has provided further rationale for pharmacologic modulation of the LAG-3 axis in cancer patients. INCAGN02385 is an Fc-engineered IgG1κ antibody chosen for development based on its high-affinity binding to human LAG-3, cross-reactivity with cynomolgus monkey LAG-3, and ability to potently block LAG-3 binding with its MHC class II ligand. INCAGN02385 also enhances T cell responsiveness to TCR stimulation alone or in combination with PD-1/PD-L1 axis blockade. Evaluation of INCAGN02385 in cynomolgus monkeys was well-tolerated and demonstrated the expected pharmacokinetic profile. Altogether, these data support assessment of INCAGN02385 in patients with advanced or metastatic solid tumors. Citation Format: David Savitsky, Rebecca Ward, Christina Riordan, Cornelia Mundt, Shawn Jennings, Joe Connolly, Mark Findeis, Michele Sanicola, Dennis Underwood, Horacio Nastri, Peggy Scherle, Gregory Hollis, Reid Huber, Robert Stein, Marc van Dijk, Nicholas S. Wilson. INCAGN02385 is an antagonist antibody targeting the co-inhibitory receptor LAG-3 for the treatment of human malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3819.