First-in-human study of the dual A

backgroundAdenosine is a key driver of an immunosuppressive tumor microenvironment. Elevated extracellular adenosine levels in the tumor microenvironment contribute to therapeutic resistance via A PATIENTS AND

methodsThis phase I, open-label, first-in-human study (NCT05198349) evaluated muvadenant in adult patients with advanced solid malignancies (Eastern Cooperative Oncology Group performance status ≤1). Primary objectives were determination of maximum tolerated dose and recommended dose for expansion of muvadenant. Additional objectives included pharmacokinetics, pharmacodynamics and early signs of efficacy.

resultsOverall, 15 patients were evaluated across four dose levels (DLs) of muvadenant monotherapy provided twice daily (bd): 150 mg (n = 3), 300 mg (n = 3), 450 mg (n = 6), and 600 mg (n = 3). Dose-limiting toxicities were reported in two patients [grade 4 blood creatinine phosphokinase increased (450-mg DL, n = 1) and grade 3 lipase increased (600-mg DL, n = 1)]. Fatigue and nausea were the most common adverse events (n = 5 each, 33.3% each), while nausea was the most common muvadenant-related adverse event (n = 4, 26.7%). Two deaths were reported, both attributed to disease progression >30 days after treatment end. Best overall response of stable disease was recorded in three patients, including one patient with a stable disease of 12.6 months at the 150-mg DL. Median progression-free survival was 1.3 months (95% confidence interval 1.2-2.6). The potential recommended dose for expansion was 450-mg bd, and the maximum tolerated dose was not established due to early closure of the study.

conclusionsMuvadenant was generally well tolerated; however, no antitumor activity was observed. A potential dose-response could not be determined due to limited number of patients per DL.