Date: 2015-10-28
Type of information: Treatment of the first patient
phase: 3
Announcement: treatment of the first patient
Company: Astellas Pharma (Japan)
Product: ASP2215 - gilteritinib
Action
mechanism: kinase inhibitor/tyrosine kinase inhibitor/FLT3 inhibitor/AXL inhibitor. Gilteritinib is a receptor tyrosine kinase inhibitor of FLT3 and AXL, which are involved in the growth of cancer cells. 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 acute myeloid leukemia. Gilteritinib was discovered through a research collaboration with Kotobuki Pharmaceutical and Astellas has exclusive global rights to develop, manufacture and potentially commercialize gilteritinib.
Disease: acute myeloid leukemia
Therapeutic area: Cancer - Oncology
Country: Belgium, Italy, Republic of Korea, Taiwan, USA
Trial
details: The purpose of this phase 3 study is to determine the clinical benefit of ASP2215 therapy in patients with FMS-like tyrosine kinase (FLT3) mutated acute myeloid leukemia who are refractory to or have relapsed after first-line AML therapy as shown with overall survival compared to salvage chemotherapy. This study will also determine the overall efficacy in event-free survival (EFS) and complete remission (CR) rate of ASP2215 compared to salvage chemotherapy. The study will enroll 369 patients with FLT3 activating mutation in bone marrow or whole blood, as determined by central lab, AML who are refractory to or have relapsed after first-line AML therapy. Subjects will be randomized in a 2:1 ratio to receive gilteritinib (120 mg) or salvage chemotherapy consisting of LoDAC (low-dose cytarabine), azacitidine, MEC (mitoxantrone, etoposide, and intermediate-dose cytarabine), or FLAG-IDA (fludarabine, cytarabine, and granulocyte colony-stimulating factor with idarubicin). The primary endpoint of the trial is OS. (NCT02421939)
Latest
news: * On October 28, 2015, Astellas Pharma announced dosing of the first patient in a randomized Phase 3 registration trial of gilteritinib (ASP2215) versus salvage chemotherapy in patients with relapsed or refractory acute myeloid leukemia (AML). The primary endpoint of the trial is overall survival. The gilteritinib Phase 3 trial follows a Phase 1/2 trial, which evaluated doses from 20 to 450 mg once daily. A parallel multi-dose expansion cohort was initiated based on the efficacy seen in the dose escalation phase. Preliminary data from the Phase 1/2 trial presented at the 2015 American Society of Clinical Oncology annual meeting demonstrated a 57.5 percent overall response rate and a 47.2 percent composite Complete Response (CR) rate (CR + CR with incomplete platelet recovery + CR with incomplete hematologic recovery) in 106 patients with FLT3 mutations who received 80 mg and higher doses. Median duration of response was 18 weeks across all doses and median OS was approximately 27 weeks at 80 mg and above in FLT3 mutation positive patients. Common drug-related adverse events (> 10%) observed in the study were diarrhea (13.4%), fatigue (12.4%) and AST increase (11.3%). At the 450 mg dose, two patients reached dose-limiting toxicity (grade 3 diarrhea and ALT/AST elevation) and the maximum tolerated dose was determined to be 300 mg.
