MIRROS: A Randomized, Placebo-Controlled, Phase III Trial of Cytarabine ± Idasanutlin in Relapsed or Refractory Acute Myeloid Leukemia
Pau Montesinos, Benjamin M. Beckermann, Olivier Catalani, Jordi Esteve, Katia Gamel, Marina Konopleva, Giovanni Martinelli, Annabelle Monnet, Cristina Papayannidis, Aaron Park, Christian Récher, Rebeca Rodríguez‐Veiga, Christoph Röllig, Norbert Vey, Andrew H. Wei, Sung‐Soo Yoon, Pierre Fenaux
Abstract
Patients with refractory or relapsed acute myeloid leukemia (R/R AML) have a poor prognosis, with a high unmet medical need. Idasanutlin is a small-molecule inhibitor of MDM2, a negative regulator of tumor suppressor p53. By preventing the p53–MDM2 interaction, idasanutlin allows for p53 activation, particularly in patients with TP53 wild-type (WT) status. MIRROS (NCT02545283) is a randomized Phase III trial evaluating idasanutlin + cytarabine versus placebo + cytarabine in R/R AML. The primary end point is overall survival in the TP53-WT population. Secondary end points include complete remission rate (cycle 1), overall remission rate (cycle 1) and event-free survival in the TP53-WT population. MIRROS has an innovative design that integrates a stringent interim analysis for futility; continuation criteria were met in mid-2017 and accrual is ongoing. Trial registration number: NCT02545283