Astellas, Ambit Biosciences announce interim results from AC220 Phase 2 trial against AML

Ambit Biosciences Corporation and Astellas Pharma Inc. announced today results from a planned interim analysis in an ongoing Phase 2 study evaluating AC220, a potent and selective FLT3 inhibitor.  The study is evaluating AC220 as an oral, once-a-day, monotherapy treatment in acute myeloid leukemia (AML) in 240 patients with FLT3-ITD activating mutations who have relapsed or are refractory to other treatments, including chemotherapy and hematopoietic stem cell transplant (HSCT).  The data from this analysis was presented in an oral session at the 16^th Annual Congress of the European Hematology Association (EHA) in London.

"AML patients who relapse or fail to respond to front-line chemotherapy have poor prognoses, and patients that harbor mutations in the FLT3 kinase are at an increased risk of disease relapse," said Mark Levis, MD, PhD, Associate Professor, Oncology and Medicine, Division of Hematologic Malignancies, Johns Hopkins, Baltimore, Maryland, and an investigator in the Phase 2 study. "Once these patients progress, the options available to them are limited, poorly tolerated by the majority of patients, and often ineffective.  We presently lack an acceptable standard of care for AML patients with FLT3-ITD activating mutations once they fail front-line treatment."

This interim analysis reported on clinical response and safety in a subset of patients from the ongoing Phase 2 open-label, single-arm, multi-center study conducted in the United States and Europe.  Safety data was reported on 62 patients and clinical response data was reported on a group of 53 patients who met the efficacy evaluable (EE) criteria.  Patients included in the analysis were either greater than or equal to  60 years old and relapsed or refractory to first-line chemotherapy (Cohort 1).

The co-primary end points of the study are composite complete remission rate (CRc) and complete remission rate in the first 84 days.  CRc is defined as the sum of complete remission (CR), complete remission with incomplete platelet recovery (CRp), and complete remission with incomplete hematologic recovery (CRi).  In the efficacy evaluable population, there was a composite complete response (CRc) rate of 45% for all patients, and 41% and 48% in Cohort 1 and Cohort 2, respectively, with the majority of CRc cases represented by CRi, with no CRs observed, in the first 84 days.  Notably, a CRc rate of 62% was achieved in patients who were refractory to the prior line of treatment.

No treatment-related deaths have been reported at the time of the analysis.  The most common treatment-related adverse events included nausea, vomiting, fatigue, and febrile neutropenia.  Several cases of asymptomatic QTc prolongation were reported early in the study, but most resolved following a dose adjustment, and no Grade 4 cases have been reported.  Management of other adverse events is also being explored with dose modifications in the ongoing study.