MEI Pharma, Inc., an oncology company focused on the clinical development of novel therapies for cancer, has reported results from a phase I first-in-human, single-agent clinical study of its investigational mitochondrial inhibitor drug candidate, ME-344, in patients with refractory solid tumours. These results were presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston, indicated that five of 21 evaluable patients treated with ME-344 experienced progression free survival (34 to 61+ weeks) that was at least twice the duration of their last prior treatment before entry into the study.

In addition, the presentation highlighted that one of these five patients, a heavily pre-treated patient with small cell lung cancer, achieved a confirmed partial response. The patient received his first treatment of ME-344 in August 2012 and has now been on study for more than 61 weeks. His June 2013 scans showed a decrease of 32 per cent in target lesions, which was confirmed in his most recent scans (August 2013). This patient and three others remain on study and continue weekly dosing.

“The observed radiographic partial response is promising, particularly in such a difficult-to-treat disease as small cell lung cancer,” said presenter and co-investigator Jeffrey R Infante, MD, director, Drug Development at Sarah Cannon Research Institute and Tennessee Oncology. “In addition to tumour shrinkage, this patient has also demonstrated symptomatic improvement while on study, including decreased cough, shortness of breath and improved performance status. The results of this single agent phase I study are encouraging and further clinical development of ME-344 is warranted.”

ME-344 was generally well tolerated at doses equal to or less than 10 mg/kg delivered on a weekly schedule for extended durations. Dose limiting toxicities were observed at both the 15 and 20 mg/kg dose levels, consisting primarily of Grade 3 peripheral neuropathy. Other medically significant adverse events observed in single patients included angina and QTc prolongation at the 10 mg/kg dose.

“We are encouraged by the results from this first-in-human study of ME-344,” said Robert D Mass, MD, chief medical officer of MEI Pharma. “Not only did the trial show evidence of clinical activity, but the primary dose limiting toxicity was consistent with the proposed mechanism of action of ME-344, namely mitochondrial inhibition, suggesting on-target activity. Based on these findings, we are now actively preparing for a phase Ib clinical trial of ME-344 in combination with Hycamtin (topotecan) in small cell lung cancer and ovarian cancer, which we expect to initiate during the second quarter of 2014.”

The phase Ib trial will be designed to evaluate the safety and tolerability of ME-344 in combination with Hycamtin in a total of 45 patients with either small cell lung cancer or ovarian cancer. Hycamtin is a chemotherapy approved by the US Food & Drug Administration for the treatment of small cell lung cancer and ovarian cancer, as well as cervical cancer.

ME-344 is MEI Pharma’s isoflavone-derived mitochondrial inhibitor drug candidate. In preclinical studies, ME-344 has been shown to cause caspase-independent cell death in multiple human tumor cell lines, including ovarian cancer stem cells, by interfering with mitochondrial energy generation. In April 2013, Ayesha Alvero, MD, Yale University School of Medicine, presented data at the American Association for Cancer Research Annual Meeting showing the ability of ME-344 to decrease tumor burden and delay recurrence in a pre-clinical in vivo model of recurrent epithelial ovarian cancer, the most lethal of all gynecologic malignancies.

MEI Pharma owns exclusive worldwide rights to ME-344.