190P Combination of IPH5201, a blocking antibody targeting the CD39 immunosuppressive pathway, with durvalumab and chemotherapies: Preclinical rationale

CD39 is an extracellular ectonucleotidase highly expressed in the tumor microenvironment (TME) that, sequentially with CD73, contributes to production of adenosine (Ado), via hydrolysis triphosphate (ATP). IPH5201 a blocking anti-CD39 monoclonal antibody (mAb) that may promote antitumor immunity by accumulating immunostimulatory ATP released necrotic cells and reducing immunosuppressive Ado levels TME. Targeting pathway has recently been reported improve Durvalumab (D) efficacy early-stage NSCLC patients, through use Oleclumab, anti-CD73 mAb. In first-in-human study (NCT04261075), was well tolerated alone or combination D. Here we explored preclinical anti-PD-L1 chemotherapies (CT). expression assessed early late stage biopsies. vitro, CT were for their ability induce release dying evaluated its accumulate ATP. vivo, human (hu) Knock-In (KI) mice used engraft syngeneic tumors evaluate mouse (mo) version (moIPH5201) anti-PD-L1. both squamous adenocarcinoma subtypes no difference according disease. model engrafted huCD39KI mice, moIPH5201 able decrease enzymatic activity lower level situ. induced Finally, improved anti-tumor gemcitabine combination. shown block activity, increase TME finally models. Altogether, profile data support clinical evaluation D patients.