One of Takeda's experimental cancer therapies has been tested in a small group of advanced lymphoma patients, offering a snapshot of "modest" efficacy that could be amplified in earlier stage patients and in combination with other drugs.
A team at MD Anderson in Texas undertook the dose-escalating study of pevonedistat, recruiting 44 patients for the Phase I study. The drug, formerly MLN4924 at Millennium Pharmaceuticals (now Takeda Oncology), is an NEDD8-activating enzyme inhibitor which alters the way cancer cells repair damaged DNA.
According to the team, three patients achieved a partial response: one with relapsed nodular sclerosis Hodgkin lymphoma, one with relapsed diffuse large B-cell lymphoma, and one with relapsed peripheral T-cell lymphoma. Another 30 patients, 17 with lymphoma and 13 with multiple myeloma, achieved stable disease. The results were published in the journal Clinical Cancer Research.
"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," says Dr. Jatin J. Shah, an 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. "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."
This isn't the first small Phase I study for this drug. Back in 2010 Millennium reported that the drug was linked to a complete response among 4 of 24 patients enrolled in a trial for acute myeloid leukemia, offering more intriguing signs of limited activity.