MEI Pharma, Inc., an oncology company focused on the clinical development of novel therapies for cancer, has dosed its first patient in a phase II clinical trial of Pracinostat, the company's investigational oral histone deacetylase (HDAC) inhibitor, in patients with myelodysplastic syndrome (MDS) who either failed to respond or maintain a response to a hypomethylating agent (HMA) alone.
"We are very excited about getting this study underway," said Robert D Mass, chief medical officer of MEI Pharma. "This represents the third in a series of phase II clinical trials we are conducting with Pracinostat in combination with HMAs in an attempt to establish the clinical benefit of selectively combining two epigenetic modifiers. The primary objective in this refractory MDS trial is to determine if the addition of Pracinostat to Vidaza or Dacogen can improve clinical responses or rescue previous responses achieved with a HMA alone. We look forward to reporting preliminary data from all three phase II trials of Pracinostat later this year."
This two-stage trial of Pracinostat is expected to enroll up to a total of 76 patients into two groups: patients who have had disease progression or have relapsed following a clinical response to either Vidaza or Dacogen therapy and patients with stable disease who failed to respond to their initial HMA therapy. If at any time two or more responses are observed in the first 29 patients of each group, that group will continue to enroll an additional nine patients in the second stage, for a total of up to 38 evaluable patients per group. Preliminary data from this open-label trial is anticipated by December 2014.
The primary endpoint of the trial is clinical improvement rate, defined as the proportion of patients with complete remission (CR), partial remission (PR) and hematologic improvement (HI). Secondary endpoints include overall response rate, CR rate, HI rate, duration of response, progression-free survival, time to progression and overall survival. Dr Guillermo Garcia-Manero of the MD Anderson Cancer Centre is the study's Principal Investigator.
Meanwhile, MEI Pharma remains on track to fully enroll its randomized, placebo-controlled Phase II trial of Pracinostat in combination with Vidaza in patients with previously untreated intermediate-2 or high-risk MDS by June 2014, with topline data expected by December 2014.
In addition, the Company continues to enroll patients in a two-stage phase II trial of Pracinostat in combination with Vidaza in elderly patients with newly diagnosed acute myeloid leukemia (AML). If at any time three or more responses are observed in the first 27 patients, the trial will continue to enroll an additional 13 patients in the second stage, for a total of up to 40 evaluable patients. Preliminary data from this open-label trial is also anticipated by December 2014.
Pracinostat is an orally available HDAC inhibitor that has been tested in a number of phase I and phase II clinical trials in advanced hematologic disorders and solid tumour indications. Pracinostat has been generally well tolerated in more than 200 adult and pediatric patients to date, with readily manageable side effects that are often associated with drugs of this class, including fatigue. In a phase I dose-escalation trial, Pracinostat demonstrated evidence of single-agent activity in elderly AML patients, including two out of 14 (14%) who achieved a CR, with durable responses persisting 206+ and 362 days, respectively. In addition, results from a pilot Phase II study of Pracinostat in combination with Vidaza in patients with advanced MDS showed an overall response rate of 90% (nine out of 10), including eight patients who achieved either a CR or a CR with incomplete blood count recovery (CRi).
MEI Pharma owns exclusive worldwide rights to Pracinostat.