Astellas Pharma Europe has announced that preliminary data from a Phase 1/2 triala on the safety, tolerability and efficacy of ASP2215, a selective inhibitor of FLT3/AXL, in patients with relapsed or refractory (R/R) acute myeloid leukaemia (AML) were presented at the 20th Congress of the European Hematology Association in Vienna, Austria.1

Preliminary data from the Phase 1/2 trial demonstrated a 57.5 percent overall response rate and a 47.2 percent composite complete remission (CR) rate (CR + CR with incomplete platelet recovery + CR with incomplete haematologic recovery) in 106 patients with FLT3 mutations who received 80 mg and higher doses.1 A plasma inhibitory activity assay also confirmed sustained FLT3 inhibition consistently in patients receiving doses of 80 mg and above.1

These data were first presented at the American Society of Clinical Oncology's (ASCO) annual meeting in Chicago on 30 May 2015. Additional preliminary data from the Phase 1/2 trial presented at ASCO and EHA also showed that the median duration of response was 18 weeks across all doses and median overall survival was approximately 27 weeks at 80 mg and above in FLT3 mutation positive patients.1 At EHA, preferable pharmacokinetics (PK) profile was also presented.

"ASP2215 is an exciting therapeutic development for relapsed and refractory acute myeloid leukaemia patients with FLT3 mutations, where there is a significant unmet need," said Alexander Perl M.D., Assistant Professor in the Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA. "Treatment with ASP2215 has demonstrated a high overall response rate and promising survival in this group of patients who have highly aggressive leukaemia and historically fared poorly with standard chemotherapy. ASP2215 is quite well tolerated in this setting and provides patients a low toxicity, effective option either to bridge to transplant with curative intent or to maintain quality of life for extended periods."

ASP2215 is a receptor tyrosine kinase inhibitor of FLT3 and AXL involved in the growth of cancer cells.1 ASP2215 has demonstrated inhibitory activity against FLT3 internal tandem duplication (ITD) as well as tyrosine kinase domain (TKD), two common types of FLT3 mutations1 that are seen in up to one third of patients with AML.1,2 Both of these mutations are typically associated with a poor prognosis.3

"At Astellas Oncology, we are focused on developing targeted therapies for hard-to-treat cancers with few therapeutic options, such as AML," said Claire Thom, Pharm.D., Senior Vice President and Oncology Therapeutic Head, Astellas Pharma Global Development, Inc. "We are very excited about these results as they indicate that ASP2215 may be a therapeutic option in this underserved patient population. We look forward to moving this candidate into Phase 3 trials to further explore the full potential of the compound for patients suffering from AML."

The ASP2215 Phase 1/2 trial design followed a 3+3 escalation and evaluated doses from 20 to 450 mg once daily.1 A parallel multi-dose expansion cohort was initiated based on the efficacy seen in dose escalation.1 A total of 198 patients were enrolled in the study, 24 in the dose escalation and 174 in the dose expansion cohorts.1 At the 450 mg dose, two patients reached dose limiting toxicity (grade 3 diarrhoea and ALT/AST elevation), and the maximum tolerated dose was determined to be 300 mg.1

A randomised Phase 3 trial of ASP2215 at 120 mg per day in relapsed and refractory AML patients is planned. For more information, visit https://clinicaltrials.gov/ct2/show/NCT02421939.

ASP2215 was discovered through a research collaboration with Kotobuki Pharmaceutical Co., Ltd., and Astellas has exclusive global rights to develop, manufacture and potentially commercialise ASP2215.