New phase II data demonstrates significant activity of quizartinib in relapsed or refractory acute myeloid leukaemia (AML) patients1,2

Astellas Pharma Inc. (Tokyo: 4503, Astellas) and Ambit Biosciences Corporation today announced the results from a completed phase II study with the investigational FLT3 inhibitor, quizartinib (AC220), as an oral monotherapy treatment regimen in patients with relapsed or refractory acute myeloid leukemia (AML).1,2

These data from two study cohorts (patients aged ≥ 60 years with AML relapsed in <1 year or refractory to 1st-line chemotherapy; patients aged ≥ 18 years with AML relapsed or refractory to second line, salvage chemotherapy or relapsed after HSCT) were presented at the American Society of Haematology (ASH) meeting in Atlanta, Georgia. Combined results from the two cohorts included:

• Approximately 50 percent of FLT3-ITD positive patients achieved a composite complete response (CRc = complete remission (CR) + complete remission with incomplete platelet recovery (CRp) + complete remission with incomplete hematologic recovery (CRi))1,2
• Additionally, around one in three FLT3-ITD positive patients in the cohort that were heavily pre-treated (i.e. had relapsed or were refractory after two prior lines of treatment or after a prior HSCT) received a potentially curative HSCT following treatment with quizartinib2

“AML is amongst the most challenging haematological malignancies to treat, and patients with activating FLT3 mutations have a particularly poor prognosis and often relapse or are refractory to current treatment options,” said Dr Jorge Cortes, the University of Texas M.D. Anderson Cancer Center. “There is a significant unmet need for new approaches that can help to stabilise the disease and provide additional time for patients to access potentially curative stem cell transplant. These data are exciting as quizartinib is the only single agent to date that has demonstrated encouraging activity in this challenging patient population.”

AML is considered to be the most common form of myeloid leukaemia in adults, affecting between 5 and 8 people in every 100,000 in Europe.3 Overall mortality is high (between 4 and 6 in every 100,000)3. Mutations of FLT3 have been detected in approximately 30% of AML patients, 24% of these mutations have been found to be internal tandem duplication (ITD) mutations. Patients with FLT3 mutations tend to have a poor prognosis4.

In general, the prognosis of AML patients after relapse is poor and treatment options unsatisfactory. The overall aim of treatment and best hope for refractory or heavily pre-treated patients is HSCT5.

In addition to the clinical benefit observed in FLT3-ITD positive patients, these data demonstrated substantial evidence of activity in FLT3-ITD negative patients, with approximately one in three patients achieving a CRc and a comparable percentage receiving HSCT as in the FLT3-ITD positive group.2

Safety findings in the study were consistent with previous studies; primarily gastrointestinal, myelosuppression and QT prolongation. These were generally mitigated with dose modifications so approximately 10% of patients experienced an adverse event (AE) that resulted in treatment discontinuation.1,2

References

1. Cortes JE, Perl AE, Dombret H, et al. Final Results of a Phase 2 Open-Label, Monotherapy Efficacy and Safety Study of Quizartinib (AC220) in Patients ≥ 60 Years of Age with FLT3 ITD Positive or Negative Relapsed/Refractory Acute Myeloid Leukemia (Abstract #43). Abstract presented at the 54th Annual Meeting of the American Society of Hematology (ASH), Atlanta, Georgia: https://ash.confex.com/ash/2012/webprogram/Paper53990.html
2. Levis MJ, Perl AE, Dombret H, et al. Final Results of a Phase 2 Open-Label, Monotherapy Efficacy and Safety Study of Quizartinib (AC220) in Patients with FLT3-ITD Positive or Negative Relapsed/Refractory Acute Myeloid Leukemia After Second-Line Chemotherapy or Hematopoietic Stem Cell Transplantation (Abstract #673). Abstract presented at the 54th Annual Meeting of the American Society of Hematology (ASH), Atlanta, Georgia: https://ash.confex.com/ash/2012/webprogram/Paper54037.html
3. Fey M, Dreyling M and on behalf of the ESMO Guidelines Working Group. Acute myeloblastic leukemia in adult patients: ESMO Clinical Recommendations for diagnosis, treatment and follow-up. Ann Oncol (2009) 20 (suppl 4): iv100-iv101
4. Gilliland DG, Griffin JD. The roles of FLT3 in hematopoiesis and leukemia. Blood 2002; 100: 1532-1542
5. Döhner H et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 2010; 115(3):453-474