Results from a phase 1 clinical trial suggest that pevonedistat, a NEDD8-activating enzyme inhibitor, is safe, tolerable, and has some anticancer activity in heavily pretreated patients with relapsed/refractory lymphoma, according to a new study published in the journal Clinical Cancer Research.1

For the study, researchers enrolled 44 patients, of which 17 had relapsed/refractory multiple myeloma and 27 had relapsed/refractory lymphoma. Escalating doses of pevonedistat were administered on days 1, 2, 8, and 9 (schedule A) or days 1, 4, 8, and 11 (schedule B) of each 21-day cycle.

Results showed that 3 patients with lymphoma achieved a partial response, while 17 with lymphoma and 13 with multiple myeloma achieved stable disease.

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In regard to safety, the most common serious adverse events were anemia, neutropenia, and pneumonia.

“The most important findings from our study are that pevonedistat hits its target in cancer cells in patients, can be given safely, and has modest activity in heavily pretreated patients with relapsed/refractory lymphoma, suggesting that we are on the right path,” Jatin J. Shah, MD, associate professor of medicine, director of myeloma clinical/translational research, and director of the lymphoma/myeloma fellowship program in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center in Houston, said.

Of note, researchers found that the investigational drug hit its target in cancer cells at low doses, which may ultimately increase the risk-to-benefit ratio of the drug.

“Although pevonedistat had modest activity as a single agent treatment, we expect greater activity when it is given in combination with standard therapy, and there are a number of combinations currently in clinical testing for acute myeloid leukemia,” Shah said.


1. First-in-class investigational therapeutic shows early promise for lymphoma patients [news release]. EurekAlert! web site. Published November 11, 2015. Accessed November 11, 2015.