Phase I study of daily and weekly regimens of the orally administered MDM2 antagonist idasanutlin in patients with advanced tumors
Antoine Italiano, Wilson H Miller, Jean-Yves Blay, Jourik A Gietema, Yung-Jue Bang, Linda R Mileshkin, Hal W Hirte, Brian Higgins, Steven Blotner, Gwen L Nichols, Lin Chi Chen, Claire Petry, Qi Joy Yang, Christophe Schmitt, Candice Jamois, Lillian L Siu
INVESTIGATIONAL NEW DRUGS | SPRINGER | Published : 2021
Aim The oral MDM2 antagonist idasanutlin inhibits the p53-MDM2 interaction, enabling p53 activation, tumor growth inhibition, and increased survival in xenograft models. Methods We conducted a Phase I study of idasanutlin (microprecipitate bulk powder formulation) to determine the maximum tolerated dose (MTD), safety, pharmacokinetics, pharmacodynamics, food effect, and clinical activity in patients with advanced malignancies. Schedules investigated were once weekly for 3 weeks (QW × 3), once daily for 3 days (QD × 3), or QD × 5 every 28 days. We also analyzed p53 activation and the anti-proliferative effects of idasanutlin. Results The dose-escalation phase included 85 patients (QW × 3, n =..View full abstract
This study was sponsored by F. Hoffmann-La Roche, Ltd. The study sponsor participated in the concept, design, conduct, analysis and interpretation of the study and results, and in the writing of this report.