Mirati Therapeutics Doses First Patient in Investigator-Sponsored Phase 2 Study of Mocetinostat in Non-Hodgkin's Lymphoma

Mirati Therapeutics, Inc.

today announced that Memorial Sloan Kettering Cancer Center in New York has dosed the first patient in an investigator-sponsored Phase 2 clinical trial of mocetinostat in patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). The trial will enroll patients whose tumors have mutations or deletions of the CREBBP and/or EP300 genes. "Genetic sequencing is becoming more widely used to select patients for specific targeted therapy for cancer. We are excited to begin testing mocetinostat, an oral HDAC inhibitor, in patients with DLBCL and FL that harbor CREBBP and EP300 genetic alterations," said Anas Younes, M.D., medical oncologist, chief of Memorial Sloan Kettering's Lymphoma Service, and principal investigator in the study. "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." Mocetinostat is a potent and selective inhibitor of HDAC 1, 2, 3 and 11, which are master regulators of cancer gene expression. Mocetinostat is being developed as a single agent treatment targeting mutations and deletions of the histone acetyltransferase (HAT) genes CREBBP and EP300. These genetic alterations are implicated in the pathogenesis and progression of DLBCL, FL, as well as bladder cancer and other solid tumor types. In preclinical models, mocetinostat reverses aberrant acetylation resulting from HAT mutations and is predicted to decrease tumors resulting in clinical responses in patients. The CREBBP and EP300 mutations are prevalent in up to 25% of patients with DLBCL and FL. "Clinical studies of mocetinostat showed responses in a subset of patients with DLBCL," said Charles M. Baum, M.D., Ph.D., president and CEO of Mirati. "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." The open-label Phase 2 study of mocetinostat is expected to enroll 54 patients with relapsed/refractory non-Hodgkin's lymphoma (NHL): 27 patients with diffuse large B-cell lymphoma and 27 with follicular lymphoma. The purpose of this trial is to determine the therapeutic efficacy of mocetinostat in selected DLBCL and FL patients with CREBBP and/or EP300 genetic alterations. Eligible patients will be treated with mocetinostat and monitored for overall response, event free survival, and duration of response. Patients are expected to receive mocetinostat at a dose of 90 mg orally three times per week on a 28 day schedule. Additional information about this clinical trial of mocetinostat is available at www.clinicaltrials.gov using identifier: NCT02282358.