Astellas, Ambit announce results from quizartinib Phase 2 study on acute myeloid leukemia

Published on December 11, 2012 at 7:20 AM · No Comments
    • For FLT3-ITD positive patients:
      • The CRc rate was 46 percent (6 percent CR+CRp  and 40 percent CRi),
      • The median duration of CRc was 12.1 weeks, which was likely impacted by a high percentage (37 percent) of patients who were bridged to HSCT,
      • An additional 27 percent of patients achieved a PR,
      • Of those refractory to last prior AML therapy, 75 percent achieved at least a PR  with quizartinib,
      • The rate of HSCT after quizartinib use was 37 percent, which represents clinical benefit in this heavily pretreated patient population,
      • The median overall survival was 22.9 weeks, with the impact of bridge to HSCT shown by a median overall survival of 33.3 weeks in those who received a subsequent HSCT after quizartinib compared to median overall survival of 17.7 weeks in those patients who did not undergo a subsequent HSCT,
      • Twenty-three patients (23 percent) are considered "long-term survivors" given they remained alive for more than 12 months
    • For FLT3-ITD negative patients:
      • The CRc rate was 32 percent (6 percent CR+ CRp and 26 percent CRi),
      • The median duration of CRc was 7.0,weeks, which was likely impacted by a high percentage (37 percent) of patients who were bridged to a HSCT,
      • An additional 16 percent of patients achieved a PR,
      • Of those refractory to their last AML therapy, 48 percent achieved at least a PR with quizartinib,
      • The rate of HSCT after quizartinib use was 37 percent, which represents clinical benefit in this heavily pretreated patient population,  
      • The median overall survival was 25.6 weeks,
      • Ten patients (26 percent) are considered "long-term survivors" given they remained alive for more than 12 months
    • The most common treatment-emergent AEs were nausea (53 percent), vomiting (41 percent), febrile neutropenia (38 percent), diarrhea (37 percent), anemia (34 percent), QT interval prolongation (27 percent) and fatigue (24 percent).  QT interval prolongations were asymptomatic, transient, and there were no Grade 4 events or deaths associated with QT prolongation. A total of 25 patients (18 percent) experienced an AE resulting in discontinuation of quizartinib, with the most common AE leading to discontinuation being progressive disease.
    • Overall, responses (CRc) were achieved in 46 percent of heavily pretreated patients with the FLT3-ITD mutation. These responses are clinically meaningful given they allowed a high percentage (37 percent) of  patients to be bridged to a stem cell transplant, and 23 percent of the FLT3-ITD positive patients remained alive for more than 12 months (of which 61 percent received a HSCT). The potential impact of bridge to HSCT was shown in the median overall survival for patients with the FLT3-ITD mutation which was 33.3 weeks for those who had a subsequent HSCT, compared to 17.7 weeks in those patients with the FLT3-ITD mutation who did not receive a subsequent HSCT.  Nearly one-in-three patients without the FLT3-ITD mutation also responded to quizartinib and may benefit from its future use. Quizartinib is well tolerated, with gastrointestinal toxicities being the most common as well as reversible QT prolongation which was infrequently grade 3 (with no cases of grade 4 in this patient cohort) at the doses used in this trial. These data suggest that quizartinib may be an attractive option in this heavily pretreated patient population with limited therapeutic options.  The benefit of bridge to HSCT had a clear impact in improving overall survival for these patients.

    The Quizartinib Clinical Program
    As of Dec. 1, 2012, approximately 450 patients have been enrolled into clinical trials evaluating quizartinib in AML, and in addition to the Phase 2 study presented this week, other ongoing trials with quizartinib include: 

    • "An Open Label Study to Evaluate the Safety and Efficacy of Two Doses of Quizartinib in Patients With Relapsed or Refractory Acute Myeloid Leukemia (NCT01565668)"  The purpose of this Phase 2b study is to assess the safety and efficacy of additional dose strengths of quizartinib monotherapy in relapsed or refractory AML patients.  In addition to evaluating clinical response and survival, assessment of PD biomarkers and pharmacokinetics (PK) will be performed.  Patient enrollment started in May 2012, and the study is currently ongoing.
    • "A Study to Assess AC220 Given in Combination With Induction and Consolidation Therapy in Newly Diagnosed Acute Myeloid Leukemia (AML) (NCT01390337)"  The purpose of this Phase 1 study is to define the maximum tolerated dose of quizartinib when combined with induction and consolidation therapy, and as a maintenance therapy following induction and consolidation.  Patient enrollment is ongoing.
    • "A Study of AC220 Given After Transplant in Subjects With Acute Myeloid Leukemia (AML) (NCT01468467)"  The purpose of this Phase 1 study is to define the maximum tolerated dose of quizartinib when given as maintenance therapy after treatment with an allogeneic HSCT.  Patient enrollment is ongoing.

    SOURCE Ambit Biosciences

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