Phase I Study of the Novel Investigational NEDD8-Activating Enzyme Inhibitor Pevonedistat (MLN4924) in Patients with Relapsed/Refractory Multiple Myeloma or Lymphoma.

ABSTRACT:

Purpose

Evaluate the safety, pharmacokinetic profile, pharmacodynamic effects, and antitumor activity of the first-in-class investigational NEDD8-activating enzyme (NAE) inhibitor pevonedistat (TAK-924/MLN4924) in patients with relapsed/refractory lymphoma or multiple myeloma.

Experimental design

Patients with relapsed/refractory myeloma (n = 17) or lymphoma (n = 27) received intravenous pevonedistat 25 to 147 mg/m(2) on days 1, 2, 8, 9 (schedule A; n = 27) or 100 to 261 mg/m(2) on days 1, 4, 8, 11 (schedule B; n = 17) of 21-day cycles.

Results

Maximum tolerated doses were 110 mg/m(2) (schedule A) and 196 mg/m(2) (schedule B). Dose-limiting toxicities included febrile neutropenia, transaminase elevations, muscle cramps (schedule A), and thrombocytopenia (schedule B).

SUBMITTER: Shah JJ 

PROVIDER: S-EPMC5694347 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature