Phase 1 study to evaluate the effects of rifampin on pharmacokinetics of pevonedistat, a NEDD8-activating enzyme inhibitor in patients with advanced solid tumors.

ABSTRACT: Pevonedistat (TAK-924/MLN4924) is an investigational small molecule inhibitor of the NEDD8-activating enzyme that has demonstrated clinical activity across solid tumors and hematological malignancies. Here we report the results of a phase 1 study evaluating the effect of rifampin, a strong CYP3A inducer, on the pharmacokinetics (PK) of pevonedistat in patients with advanced solid tumors (NCT03486314). Patients received a single 50 mg/m² pevonedistat dose via a 1-h infusion on Days 1 (in the absence of rifampin) and 10 (in the presence of rifampin), and daily oral dosing of rifampin 600 mg on Days 3-11. Twenty patients were enrolled and were evaluable for PK and safety. Following a single dose of pevonedistat at 50 mg/m², the mean terminal half-life of pevonedistat was

SUBMITTER: Zhou X 

PROVIDER: S-EPMC9395450 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature