MEI Pharma announced a planned interim review of data supports continuation of its multicenter, investigator sponsored, study evaluating ME-344, a novel mitochondrial inhibitor, in patients with HER2-negative breast cancer. The interim study data show that ME-344 was generally well-tolerated and, consistent with previous preclinical data, demonstrate the potential to reverse resistance to antiangiogenic therapy. Based on the interim results, it was determined that completion of enrollment of the clinical study of ME-344 in combination with bevacizumab (marketed as Avastin) is warranted.
"The interim data are very encouraging and I look forward to an opportunity to present the results at a medical meeting later this year," said the study principal investigator, Miguel Quintela-Fandino, M.D., Ph.D., Director of the Clinical Research Program, Centro Nacional De Investigaciones Oncologicas, Madrid, Spain.
Inhibition of mitochondrial adenosine triphosphate (ATP) with drug candidates such as ME-344 may have significant potential in combination with antiangiogenic agents. Antiangiogenics are widely used biologic agents in oncology, but acquired resistance to antiangiogenics is a major problem in cancer therapeutics. Antiangiogenics reduce the rate of glycolysis as a mechanism to block tumor growth, however sustained tumor growth may be achieved via a shift to an alternative metabolic energy source such as mitochondrial ATP. In such cases of tumor plasticity in the presence of treatment with antiangiogenics, targeting the alternative metabolic source would open an important therapeutic opportunity.
The study is a multicenter, investigator sponsored, randomized, open label, clinical trial evaluating ME-344 in a total of 40 patients with HER2-negative breast cancer in combination with the VEGF inhibitor bevacizumab (marketed as Avastin). Patients are randomized one-to-one to either ME-344 plus Avastin or saline plus Avastin. The primary efficacy endpoint is inhibition of cell proliferation as measured by Ki-67 reductions. The interim data review was predefined to take place after 20 patients were randomized.
ME-344 is a novel, tumor selective, isoflavone-derived mitochondrial inhibitor drug candidate. It directly targets the OXPHOS complex 1, a pathway involved in the production of adenosine triphosphate, or ATP, in the mitochondria. Treatment of tumor cells with ME-344 results in a rapid loss of ATP and cancer cell death. ME-344 has demonstrated evidence of single agent activity against refractory solid tumors in a Phase 1 study.