First-in-human study of the dual A2A/A2B adenosine receptor antagonist muvadenant (M1069) in patients with advanced solid tumors

BACKGROUND: receptors, showed encouraging preclinical activity. PATIENTS AND METHODS: This 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. RESULTS: Overall, 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. CONCLUSIONS: Muvadenant 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.