Abstract IA04: New developments in drugging the adenosine pathway

Abstract Adenosine is a pleiotropic immunosuppressive substance, produced mainly by the enzymes CD39 and CD73, from extracellular immunogenic ATP. Thus, CD73-rich tumors may experience decreased anti-tumor immune activity when treated with immunogenic chemotherapies (e.g., platinum-based drugs), relative to what might be possible in the absence of adenosine. From a therapeutic perspective, potential drugs that aim to interfere with the production or signaling of adenosine need to be potent and selective enough, under physiological conditions, to overcome the large amount of adenosine present in selected tumors. Recent results from several clinical studies are strongly supportive of the anti-cancer potential stemming from inhibition of the adenosine axis, when drug properties, tumor selection/setting, and combination backbones are taken into account. This presentation will briefly highlight key design elements for two such drugs, etrumadenant (a dual blocker of A2a and A2b adenosine receptors) and quemliclustat (a CD73 inhibitor), as well as recent clinical results with these agents in advanced colorectal cancer (CRC; ARC-9) and pancreatic cancer (PDAC; ARC-8), respectively. We will also describe how drug-related changes in markers of adenosine activity, as well as baseline levels of those markers, are associated with clinical outcomes in these trials. Citation Format: Juan C Jaen. New developments in drugging the adenosine pathway [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr IA04.