Mirati starts dosing in Phase II trial of mocetinostat to treat non-Hodgkin’s lymphoma

The open-label Phase II trial will enroll 54 patients with relapsed/refractory non-Hodgkin’s lymphoma (NHL): 27 patients with diffuse large B-cell lymphoma and 27 with follicular lymphoma.

Being carried out at the Memorial Sloan Kettering Cancer Center in New York, the trial will determine the therapeutic efficacy of mocetinostat in selected DLBCL and FL patients with CREBBP and/or EP300 genetic alterations.

Mocetinostat is a potent and selective inhibitor of HDAC 1, 2, 3 and 11, and is being developed as a single agent treatment targeting mutations and deletions of the histone acetyltransferase (HAT) genes CREBBP and EP300.

Memorial Sloan Kettering Lymphoma Service chief, medical oncologist and principal investigator in the study Anas Younes said: "Genetic sequencing is becoming more widely used to select patients for specific targeted therapy for cancer.

"This study will help determine if these mutations are predictive of response to mocetinostat that could lead to a new treatment option for patients with DLBCL and FL."

During the trial, eligible patients will be given mocetinostat at a dose of 90 mg orally three times per week on a 28 day schedule and they will be monitored for overall response, event free survival, and duration of response.

Mirati president and CEO Charles Baum said: "Clinical studies of mocetinostat showed responses in a subset of patients with DLBCL.

"Working closely with our investigators and reviewing emerging cancer genomics research, we’ve identified CREBBP and EP300 as potential drivers of disease progression that may be particularly susceptible to treatment with mocetinostat.

"We believe that selecting patients with these mutations will increase the benefit to these patients and may provide an accelerated path to regulatory approval."

Image: Micrograph of mantle cell lymphoma, a type of non-Hodgkin lymphoma. Terminal ileum. Photo: courtesy of Nephron.