Phase 3 LACEWING Trial Fails to Meet Primary End Point of OS in Newly Diagnosed FLT3+ AML

Based on the recommendation of an independent data monitoring committee, Astellas has halted enrollment in the trial and is reviewing the results for further actions needed.

The phase 3 LACEWING trial of the FMS-like tyrosine kinase 3 (FLT3) inhibitor gilteritinib (Xospata) plus azacitidine versus azacitidine alone in patients with newly diagnosed FLT3 mutation-positive acute myeloid leukemia (AML) who were ineligible for intensive induction chemotherapy did not meet its primary end point of overall survival (OS) at a planned interim analysis, according to Astellas Pharma, the developer of the agent.1

Based on these results, an independent data monitoring committee recommended the study be terminated for futility, citing that the results are unlikely to demonstrate a statistically significant increase in OS. Astellas indicated it has since halted enrollment in the trial and is reviewing the results for other action as needed.

"Although we are disappointed by the primary outcome of LACEWING, we are conducting a thorough review of the data and plan to share detailed results at a later date," Andrew Krivoshik, MD, PhD, senior vice president and head of the Oncology Therapeutic Area at Astellas, said in a press release. "These results do not affect other ongoing gilteritinib trials. We remain committed to our comprehensive program investigating gilteritinib across a wide range of AML patients with a positive FLT3 mutation, building on gilteritinib's earlier, positive data in patients with relapsed or refractory FLT3 mutation-positive AML."

The open-label, multicenter, randomized, phase 3 LACEWING trial was designed to evaluate the use of gilteritinib plus azacitidine versus azacitidine alone in approximately 250 patients with newly diagnosed FLT3 mutation-positive AML who are ineligible for first-line intensive induction chemotherapy.

The primary end point for the study is OS defined as the time from the date of randomization until the date of death from any cause. Key secondary end points include event-free survival, best response, complete remission, composite complete remission, and complete remission with partial hematologic recovery.

Results from the study presented at the 62nd ASH Annual Meeting and Exposition indicated that as of June 29, 2020, 15 patients had been enrolled in the safety cohort.2 Moreover, 14 patients had died and only 1 patient continued on treatment.

The median treatment duration was 6 (range, <1-34) cycles; a total of 40% (n = 6) received more than 12 cycles of treatment.

An overall composite complete remission of 67% (n = 10) was observed. Based on these data, a gilteritinib dose of 120 mg daily plus azacitidine was adopted for the randomization cohort.

As of the data cutoff date, 136 patients had been randomized, including 114 randomized to receive either gilberitinib in combination with azacitidine or azacitidine alone and 22 randomized to receive gilberitinib alone, though this arm is now closed. Median treatment duration was 4 (range, <1–31) cycles, with 40% (n = 54) having received 6 treatment cycles or more.

In total, 83 patients (61%) in the randomization cohort had died as of the data cutoff date.


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 [news release]. Tokyo. Published December 21, 2020. Accessed December 21, 2020.

2. Wang ES, Montesinos P, Minden MD, et al. Phase 3, Multicenter, Open-Label Study of Gilteritinib, Gilteritinib Plus Azacitidine, or Azacitidine Alone in Newly Diagnosed FLT3 Mutated (FLT3mut+) Acute Myeloid Leukemia (AML) Patients Ineligible for Intensive Induction Chemotherapy. Presented at the 62nd ASH Annual Meeting and Exposition. Oral abstract #27.

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