A Phase 2 trial to evaluate the safety and efficacy of zimberelimab monotherapy, domvanalimab + zimberelimab, and domvanalimab + zimberelimab + etrumadenant in front-line non-small cell lung cancer.
Adenosine is a powerful immunosuppressive substance produced inside tumors as a result of rapid cancer cell turnover and, in some cases, in connection with certain anti-tumor interventions, such as chemotherapy and radiation.
The A2a/A2b receptors, expressed on the surface of immune cells, mediate the immunosuppressive effects of adenosine.
Etrumadenant is designed to maximally inhibit the adenosine-driven impairment of tumor-infiltrating lymphocytes (mainly CD8+ T cells and NK cells) and myeloid cells (dendritic cells, macrophages), mediated by A2a/A2b, respectively. A2bR is also upregulated by certain cancer cells, such as in prostate cancer and KRAS-mutated cancers. As a result, etrumadenant may uniquely block adenosine’s immunosuppressive and cancer cell-intrinsic effects.
Developed specifically for the oncology setting, etrumadenant achieves high penetration of tumor tissue, robust potency in the presence of high adenosine concentrations, and minimal shift in potency from non-specific protein binding. Etrumadenant has demonstrated a favorable clinical safety profile with a variety of combination regimens and exhibits pharmacokinetics/pharmacodynamics consistent with once-daily dosing.
Etrumadenant is currently being evaluated in several Phase 1b/2 studies across multiple indications.
Non-small cell lung cancer, PD-L1 positive (ARC-7)
Non-small cell lung cancer, EGFRmut (ARC-4)
Castration-resistant prostate cancer (ARC-6)
Castration-resistant prostate cancer (ARC-5)
Colorectal cancer (MORPHEUS-CRC)
Colorectal cancer (ARC-3)
Pancreatic adenocarcinoma (MORPHEUS-PDAC)
Triple-negative breast cancer (ARC-2)