Pevonedistat (MLN4924), a First‐in‐Class NEDD8‐activating enzyme inhibitor, in patients with acute myeloid leukaemia and myelodysplastic syndromes: a phase 1 study

• Published in: British journal of haematology Vol. 169; no. 4; pp. 534 - 543
• Main Authors: Swords, Ronan T., Erba, Harry P., DeAngelo, Daniel J., Bixby, Dale L., Altman, Jessica K., Maris, Michael, Hua, Zhaowei, Blakemore, Stephen J., Faessel, Hélène, Sedarati, Farhad, Dezube, Bruce J., Giles, Francis J., Medeiros, Bruno C.
• Format: Journal Article
• Language: English
• Published: England 01.05.2015
• Subjects: acute myeloid leukaemia; Adult; Aged; Aged, 80 and over; Chemical and Drug Induced Liver Injury - blood; Cyclopentanes - administration & dosage; Cyclopentanes - adverse effects; Cyclopentanes - pharmacokinetics; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - adverse effects; Enzyme Inhibitors - pharmacokinetics; Female; Humans; Leukemia, Myeloid, Acute - blood; Leukemia, Myeloid, Acute - drug therapy; Male; Maximum Tolerated Dose; Middle Aged; MLN4924; Multiple Organ Failure - blood; Multiple Organ Failure - chemically induced; Myelodysplastic Syndromes - blood; Myelodysplastic Syndromes - drug therapy; NEDD8; NEDD8‐activating enzyme; pevonedistat; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Pyrimidines - pharmacokinetics; Ubiquitin-Activating Enzymes - antagonists & inhibitors; NEDD8; NEDD8-activating enzyme; pevonedistat; MLN4924; acute myeloid leukaemia
• ISSN: 0007-1048; 1365-2141; 1365-2141
• DOI: 10.1111/bjh.13323

Summary This trial was conducted to determine the dose‐limiting toxicities (DLTs) and maximum tolerated dose (MTD) of the first in class NEDD8‐activating enzyme (NAE) inhibitor, pevonedistat, and to investigate pevonedistat pharmacokinetics and pharmacodynamics in patients with acute myeloid leukaem...