Phase 2 Study of AZD2014, a Dual mTORC1/mTORC1 Inhibitor, For NF2 Patients with Progressive or Symptomatic Meningiomas

Meningiomas are common in neurofibromatosis 2 (NF2) patients with a cumulative incidence of 80% by 70 years of age. Meningiomas that progress despite surgery and radiation are an important unmet medical need for these patients. To date, no chemotherapy has demonstrated efficacy against NF2-related meningiomas. Our laboratory studies have shown that treatment of primary meningioma cells with AZD2014, a mTORC1/mTORC2 inhibitor, leads to decreased cell viability/proliferation. Thus, we hypothesize that AZD2014 will be effective in treating symptomatic or progressive meningiomas in NF2 patients. In this single arm, non-comparative, phase II trial, 18 patients will be treated with AZD2014 for recurrent or progressive intracranial meningioma. AZD2014 will be administered on a repeating basis at a dose of 125mg twice daily for two consecutive days out of every seven days (1 cycle = 28 days). Treatment will continue until disease progression or intolerable side effects. An MRI of the brain, with and without contrast, will be obtained every 12 weeks to assess for disease response or stability using volumetric measurements. In year 2, 4 additional subjects were enrolled on the study and accrual was completed well in advance of the anticipated 30 months. In year 3, subject follow up was completed and analysis of blood samples was performed. Data analysis will continue in year 4 of the study.