About this program
Lirilumab (IPH2102/BMS-986015) is a fully human monoclonal antibody that is designed to block the interaction between KIR2DL-1,-2,-3 inhibitory receptors and their ligands.
Blocking these receptors facilitates activation of NK cells and, potentially some subsets of T cells, ultimately leading to destruction of tumor cells.
Lirilumab, an anti-KIR monoclonal antibody, aims at “unblinding” NK cells and facilitating their activation by blocking their inhibitory receptors.
Lirilumab and related compounds blocking KIR receptors are licensed to Bristol-Myers Squibb Company (NYSE:BMY), for all indications.
Lirilumab has been or is currently being tested in several indications and combination settings.
Lirilumab continues to be well tolerated in monotherapy and in combination across multiple tumor indications in an exploratory clinical program with partner Bristol-Myers Squibb.
The assessment of efficacy from the ongoing exploration of doublet combinations, notably the nivolumab combination in an extended population of SCCHN patients, did not provide clear evidence of benefit to patients or an obvious development path.
Separately, full data of the EffiKIR Phase II study presented at ASH 2017 suggests that alternate dosing regimens could be worth exploring.
Discussions with Bristol-Myers Squibb regarding next steps are ongoing.
Benson et al, 2015. A phase I trial of the anti-KIR antibody IPH2101 and lenalidomide in patients with relapsed/refractory multiple myeloma Clinical Cancer Research Sohlberg et al, 2015. Imprint of 5-azacytidine on the natural killer cell repertoire during systemic treatment for high-risk myelodysplastic syndrome Oncotarget Nijhof et al, 2015. Daratumumab mediated lysis of primary multiple myeloma cells is enhanced in combination with the human anti KIR IPH2102 and lenalidomide Haematologica Kohrt et al, 2014. Anti-KIR antibody enhancement of anti-lymphoma activity of natural killer cells as monotherapy and in combination with anti-CD20 antibodies Blood Vey et al, 2012. A phase 1 trial of the anti-inhibitory KIR mAb IPH2101 for AML in complete remission Blood Schmiedel et al, 2011. Azacytidine impairs NK cell reactivity while decitabine augments NK cell responsiveness toward stimulation Int J Cancer Liu et al, 2009. DNA methylation inhibition increases T cell KIR expression through effects on both promoter methylation and transcription factors Clin Immunol. Romagné et al, 2009. Preclinical characterization of 1-7F9, a novel human anti-KIR receptor therapeutic antibody that augments natural killer-mediated killing of tumor cells Blood Gao et al, 2009. Demethylating treatment suppresses natural killer cell cytolytic activity Mol Immunol. Tang et al, 2008. Induction of MHC class I-related chain B (MICB) by 5-aza-2'-deoxycytidine Biochem Biophys Res Commun. Rohner et al, 2007. Differentiation-promoting drugs up-regulate NKG2D ligand expression and enhance the susceptibility of acute myeloid leukemia cells to natural killer cell-mediated lysis Leuk Res.