169P Immunomodulatory effects of RBS2418, an oral ENPP1 inhibitor in combination with pembrolizumab in checkpoint-refractory metastatic adrenal cancer

Abstract

ENPP1 is a type II transmembrane protein with nucleotide pyrophosphatase, and phosphodiesterase enzymatic activities and its expression is associated with poor prognosis in cancer. ENPP1 inhibition protects cGAMP and ATP from hydrolysis and reduces adenosine levels in the TME, activates APCs and increases T-cell infiltration promoting anticancer immunity. RBS2418 is a potent oral ENPP1 inhibitor. Here, we report pharmacokinetic (PK) and immunomodulatory properties of RBS2418 in combination with pembrolizumab (pembro) in a checkpoint-refractory high grade adrenal cancer with an immune-desert tumor phenotype at baseline.