Astellas Announces Updated Data from the Phase 1/2 CHRYSALIS Trial for Gilteritinib (ASP2215) in Patients with Relapsed or Refractory Acute Myeloid Leukaemia

Astellas Pharma Europe today announced that updated data from the Phase 1/2 CHRYSALIS trial, evaluating the safety, tolerability and efficacy of gilteritinib (ASP2215), an orally-administered inhibitor of FLT3/AXL in patients with relapsed or refractory (R/R) acute myeloid leukaemia (AML), were presented during an oral scientific session at the American Society of Hematology (ASH) 2015 annual meeting in Orlando.¹ Preliminary data were presented at the 20^th Congress of the European Hematology Association in June 2015 in Vienna, Austria.²

Gilteritinib has demonstrated inhibitory activity against FLT3 internal tandem duplication (ITD) as well as tyrosine kinase domain (TKD), two common types of FLT3 mutations that are seen in up to one-third of patients with AML.¹

This updated analysis of the Phase 1/2 study included 169 patients with FLT3 mutations who were treated with ≥80 mg and more (up to 450 mg) of gilteritinib. A 53% overall response rate (ORR) was demonstrated regardless of prior therapy. Additionally, a 56% ORR was observed in patients who had a FLT3-ITD mutation, and 48% ORR was observed in patients who were treated with a tyrosine kinase inhibitor (TKI) prior to the study. Median overall survival was approximately 31 weeks (95% CI: 24–35). Treatment-related adverse events (AE) reported in ≥10% of the safety population included diarrhoea (16%), fatigue (13%), and aspartate aminotransferase (AST) increase (12%). Grade ≥3 QTc prolongation was reported in 3%. Serious adverse events that occurred in ≥10% of total subjects were febrile neutropenia (n=77; 31%), disease progression (n=32; 13%), and sepsis (n=30; 12%).¹

“Long-term survival outcomes for patients of any age with acute myeloid leukemia (AML) using current treatments offer substantial room for improvement, and for patients with a mutation of the FLT3 gene, the need is even greater,” said Bob Löwenberg, M.D., professor of Hematology at Erasmus University Medical Center in Rotterdam Netherlands. “Promising therapies personalised to target specific biomarkers and with innovative mechanisms of action, such as gilteritinib, could change the outlook and prognosis for these patients.”

“We are pleased to see that gilteritinib demonstrates antileukaemic activity even in patients whose mutations have previously been associated with poor outcomes,” said Trial Investigator Jessica Altman, M.D. and associate professor of Haematology/Oncology at Northwestern University’s Feinberg School of Medicine.

“We live in an era of personalised medicine and targeted therapies, yet there is still a significant need for more effective AML treatments, particularly for patients with well-characterised FLT3 molecular defects,” said Erkut Bahceci, M.D. and executive medical director, Astellas. “Targeting both FLT3-ITD and FLT3-TKD mutations, as well as AXL, can potentially help avoid the acquired resistance seen with existing FLT3-ITD inhibitors and may increase duration of therapy.”

Notes to editors

About Acute Myeloid Leukaemia
Acute myeloid leukemia is a cancer that affects white blood cells and bone marrow.³ AML usually develops quickly, over days or weeks.³ It is most often diagnosed in older people, and is most common in people over 65 years old.³ The incidence of AML in European adults is 5-8 cases per 100,000.⁴ About two out of three AML patients who get standard induction chemotherapy with daunorubicin and cytarabine go into remission.⁵ The chance of remission depends to a large part on a person’s specific prognostic factors, such as age or the presence of certain gene or chromosome changes.⁵ Currently, available treatment options for R/R AML patients with FLT3 mutations are limited and prognosis is poor.⁶

About Astellas
Astellas Pharma Europe Ltd. operates in 40 countries across Europe, the Middle East and Africa, and is the regional business of Tokyo-based Astellas Pharma Inc. Astellas is a pharmaceutical company dedicated to improving the health of people around the world through the provision of innovative and reliable pharmaceuticals. The organisation’s focus is to deliver outstanding R&D and marketing to continue growing in the world pharmaceutical market. Astellas’ presence in Europe also includes an R&D site and three manufacturing plants. The company employs approximately 4,350 staff across these countries.

References

1. Jessica K. Altman, Alexander E. Perl, Jorge Cortes et. al., Antileukemic Activity and Tolerability of ASP2215 ≥80 mg in FLT3 Mutation-Positive Subjects with Relapsed or Refractory Acute Myeloid Leukemia: Results from a Phase 1/2, Open-Label, Dose-Escalation/Dose-Response. Study presented during an oral scientific session at the American Society of Hematology (ASH) 2015 annual meeting in Orlando, 6 Dec 2015
2. Perl A, Altman J, Cortes J, et al. Results of a first in-human, Phase 1/2 trial of ASP2215, a selective, potent oral inhibitor of FLT3/AXL, in patients with relapsed or refractory acute myeloid leukaemia. 20th Congress of the European Hematology Association, Vienna, Austria. Presentation [Abstract No. S798]
3. Cancer Research UK. The blood and acute myeloid leukaemia. Available at: http://www.cancerresearchuk.org/about-cancer/type/aml/about/the-blood-and-acute-myeloid-leukaemia (Last accessed June 2015)
4. Patient UK. Acute Myeloid Leukaemia factsheet. Available at http://www.patient.co.uk/doctor/acute-myeloid-leukaemia-pro (Last accessed June 2015)
5. American Cancer Society. Treatment response rates for acute myeloid leukemia. Available at: http://www.cancer.org/cancer/leukemia-acutemyeloidaml/detailedguide/leukemia--acute-myeloid--myelogenous--treating-response-rates. (Last accessed June 2015)
6. Grunwald MR, Levis MJ. FLT3 inhibitors for acute myeloid leukemia: a review of their efficacy and mechanisms of resistance. Int J Hematol 2013; 97(6):683-94

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Contact information

Astellas Contacts:
Emma White, +44 (0)7786 312623
Manager, Communications, EMEA
or
Red Door Unlimited
Laura Good, +44 (0)7889 757191