Exploratory Analysis of the Phase I/II CHRYSALIS Study of gilteritinib Demonstrates First Molecular Response to FLT3 Inhibitor in Acute Myeloid Leukemia
NORTHBROOK, Ill., June 6, 2017 /PRNewswire/ -- Astellas today announced data from an exploratory analysis of the Phase I/II CHRYSALIS study, which demonstrated that FLT3 mutation-positive relapsed/refractory (R/R) acute myeloid leukemia (AML) patients with molecular response had improved overall survival (OS) compared with those without a molecular response when treated with either 120 mg/day or 200 mg/day doses of gilteritinib, a FLT3/AXL inhibitor. These results, which are the first demonstration of molecular response to a FLT3 inhibitor in AML, were discussed today during an oral presentation at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 7003).
AML is a rare and aggressive type of blood cancer, driven by various chromosomal and genetic abnormalities. Mutations of the FLT3 gene, including internal tandem duplications (ITD), are present in approximately one third of AML patients.These mutations lead to constitutive activation of the tyrosine kinase receptor, thereby promoting proliferation and survival of leukemia cells and contributing to a higher relapse rate and a poor response to treatment. FLT3 tyrosine kinase domain (FLT3-TKD) mutations and AXL receptor tyrosine kinase domain mutations have been associated with resistance to early generation FLT3 inhibitors.
The exploratory analysis from the CHRYSALIS study assessed molecular response via Kaplan-Meier estimation in a subgroup of FLT3-ITD mutation-positive AML patients (n=80) who received 120 mg/day (n=34) and 200 mg/day of gilteritinib (n=46). Results demonstrated that patients who achieved a molecular response (n=20) experienced significantly prolonged OS compared to those who did not (59.6 weeks versus 28.4 weeks, respectively). Results also showed that 75% (n=15/20) of molecular responders were patients who achieved a complete composite remission. The most commonly reported adverse events (AEs) in the CHRYSALIS study safety population included diarrhea (16%), fatigue (13%), and AST increase (12%).
"Importantly, patients treated with gilteritinib who achieved molecular response experienced a substantial improvement in Overall Survival compared to those without a molecular response," said Jessica K. Altman, M.D., Robert H. Laurie Cancer Center of Northwestern University.
"We continue to be encouraged by the results from our gilteritinib clinical trial program to help those who suffer from AML, an aggressive form of blood cancer that is characterized by both genetic and resistance mutations," said Steven Benner, M.D., senior vice president and global therapeutic area head, oncology development, Astellas.
About the CHRYSALIS Study
The CHRYSALIS Study is a Phase 1/2 study with objectives of determining the safety, tolerability, pharmacokinetic profile, and antileukemic activity of gilteritinib (ASP2215) in patients with R/R AML. Gilteritinib was well tolerated and showed consistent and potent FLT3 inhibition at doses ≥80 mg/day. 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 and 48% ORR was observed in patients who were treated with a tyrosine kinase inhibitor prior to the study. Median OS was approximately 31 weeks (95% CI: 24-35). Treatment-related adverse events (AEs) reported in ≥10% of the safety population included diarrhea (16%), fatigue (13%), AST increase (12%). Grade ≥3 QTc prolongation was reported in 3% of subjects.
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