Date: 2014-10-29
Type of information: Treatment of the first patient
phase: 1b
Announcement: treatment of the first patient
Company: Mei Pharma (USA - CA)
Product: ME-344 in combination with topotecan
Action
mechanism: ME-344 is an isoflavone-based mitochondrial inhibitor drug candidate. It displays a novel mechanism of action, targeting a mitochondrial component of the terminal respiratory chain complex in rapidly proliferating cells. Treatment of tumor cells with these compounds has been shown to induce cancer cell death through the induction of DNA fragmentation and through a process known as destructive autophagy, wherein a cell consumes itself. In pre-clinical studies, ME-344 has been shown to cause cell death in multiple human tumor cell lines, including ovarian stem cells, by interfering with mitochondrial energy generation.
Disease: patients with small cell lung or ovarian cancer who failed initial therapy.
Therapeutic area: Cancer - Oncology
Country:
Trial
details: The Phase Ib study is evaluating the combination of intravenous ME-344 and topotecan (trade name Hycamtin®), a drug approved by the FDA for the treatment of small cell lung, ovarian and cervical cancers. Following the initial stage of the study, an independent Safety Committee determined the recommended Phase II dose for continued testing of ME-344 to be 10 mg/kg in combination with 4 mg/m2 of topotecan.
Latest
news: * On October 29, 2014, MEI Pharma, an oncology company focused on the clinical development of novel therapies for cancer, announced that the first patient has been dosed in the cohort-expansion stage of the Company\'s Phase Ib clinical study of investigational drug candidate ME-344 in combination with topotecan in patients with small cell lung or ovarian cancer who failed initial therapy. The cohort expansion comes after the initial stage of the study confirmed the maximum tolerated dose (MTD) of ME-344 in combination with topotecan is 10mg/kg, the same dose defined for single agent use. Now the study will enroll an additional 40 patients into two cohorts: locally advanced or metastatic small cell lung cancer and ovarian cancer. In October 2013, results from a Phase I clinical study of ME-344 were presented showing preliminary evidence of single-agent activity in patients with refractory solid tumors, including eight of 21 evaluable patients (38%) who achieved stable disease or better. Notably, one patient with small cell lung cancer achieved a confirmed partial response and remained on study for 104 weeks. ME-344 was generally well tolerated in the study 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.
