Adavosertib (AZD1775) does not prolong the QTc interval in patients with advanced solid tumors: a phase I open-label study.
Cancer chemotherapy and pharmacology
PURPOSE: Adavosertib is a small-molecule, ATP-competitive inhibitor of Wee1 kinase. Molecularly targeted oncology agents have the potential to increase the risk of cardiovascular events, including prolongation of QT interval and associated cardiac arrhythmias. This study investigated the effect of adavosertib on the QTc interval in patients with advanced solid tumors.
METHODS: Eligible patients were ≥ 18 years of age with advanced solid tumors for which no standard therapy existed. Patients received adavosertib 225 mg twice daily on days 1-2 at 12-h intervals and once on day 3. Patients underwent digital 12-lead electrocardiogram and pharmacokinetic assessments pre-administration and time-matched assessments during the drug administration period. The relationship between maximum plasma drug concentration (C
RESULTS: Twenty-one patients received adavosertib. Concentration-QT modeling of ΔQTcF and the upper limit of the 90% confidence interval corresponding to the geometric mean of C
CONCLUSION: Adavosertib does not have a clinically important effect on QTc prolongation.
CLINICALTRIALS: GOV: NCT03333824.
Någård M, Ah-See ML, Strauss J, Wise-Draper T, Safran HP, Nadeau L, et al Adavosertib (AZD1775) does not prolong the QTc interval in patients with advanced solid tumors: a phase I open-label study. Cancer Chemother Pharmacol. 2023 Aug;92(2):141-150. doi: 10.1007/s00280-023-04555-2. PMID: 37368100.