Astellas Announces Phase 3 LACEWING Trial of XOSPATA® (Gilteritinib) Plus Azacitidine Fails to Meet Overall Survival Endpoint in Newly Diagnosed FLT3mut+ AML

Compiled by Keke

On December 21, Astellas announced that XOSPATA^®The Phase 3 LACEWING trial, evaluating gilteritinib (gilteritinib) in combination with azacitidine versus azacitidine monotherapy for the treatment of patients with newly diagnosed FLT3 mutation-positive (FLT3 mut+) acute myeloid leukemia (AML), did not meet its primary endpoint of overall survival (OS) in the planned interim analysis.

An independent Data Monitoring Committee recommended terminating the study, as continuing the trial was deemed futile due to the unlikelihood of demonstrating a statistically significant improvement in overall survival. Astellas has halted the trial and is reviewing the results to determine any further actions as needed.

LACEWING (NCT02752035) is an open-label, multicenter, randomized trial designed to evaluate the efficacy of gilteritinib in combination with azacitidine versus azacitidine monotherapy in approximately 250 patients with newly diagnosed FLT3-mutated acute myeloid leukemia (FLT3mut+ AML) who are ineligible for first-line intensive induction chemotherapy. The primary endpoint is overall survival (OS), assessed over a period of up to 77 months and defined as the time from the date of randomization to treatment initiation to the date of death from any cause. Key secondary endpoints include event-free survival (EFS), best response, complete remission, composite complete remission, and complete remission with partial hematologic recovery.

The phase 3 ADMIRAL study, published in 2019, showed that the one-year survival rate was 37.1% in patients with relapsed or refractory FLT3-mutated AML treated with gilteritinib monotherapy, compared with 16.7% in those receiving chemotherapy.

Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow, representing one of the most common types of leukemia in adults and carrying the lowest survival rate among all leukemia subtypes. Approximately one-third of AML patients harbor FLT3 mutations. These mutations are associated with poorer disease-free survival and overall survival. Among patients with FLT3-mutated AML, an estimated 30%–40% are ineligible for intensive chemotherapy regimens due to age, performance status, and/or comorbidities.

Xospata is a FMS-like tyrosine kinase 3 (FLT3) inhibitor with activity against FLT3-ITD, a common driver mutation associated with high mutational burden and poor prognosis, as well as against FLT3-TKD mutations. Astellas discovered this drug through a research collaboration with Kotobuki Pharmaceutical Co., Ltd., and holds exclusive global rights for its development, manufacturing, and commercialization. Xospata has currently been approved for marketing in the United States, Japan, and selected European countries as a monotherapy for the treatment of adult patients with relapsed or refractory FLT3mut+ AML. The drug had previously been granted orphan drug status by the U.S. Food and Drug Administration (FDA) and the European Commission. Driven by growth in the Japanese and U.S. markets, Astellas’ second-quarter financial report showed that Xospata’s sales reached JPY 5.3 billion (USD 51 million), representing a year-on-year increase of 64.4%.

Although Xospata monotherapy has driven sales growth, the drug missed out on opportunities for combination therapy with chemotherapy agents, and competition in the AML market remains intense. Bristol Myers Squibb markets the intravenous formulation of azacitidine under the brand name Vidaza, and its oral formulation of azacitidine recently received U.S. FDA approval under the brand name Onureg. Meanwhile, in October, AbbVie and Roche’s BCL-2 inhibitor Venclexta (venetoclax), in combination with azacitidine, decitabine, or cytarabine, was approved for the treatment of newly diagnosed acute myeloid leukemia (AML) patients aged 75 years or older who are ineligible for intensive induction chemotherapy. These developments have posed challenges to further expanding the peak sales potential of Xospata.

Reference Source:

1.Astellas Reports XOSPATA^® (gilteritinib) in Combination with Azacitidine Did Not Meet Endpoint of Overall Survival in Newly Diagnosed FLT3 Mutation-Positive Acute Myeloid Leukemia Patients Ineligible for Intensive Induction Chemotherapy

2.Astellas' Xospata fails to meet survival goal in acute myeloid leukaemia study