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Rebecca Olin, MD, MS


Entospletinib Under Study in Phase III Trial for Newly Diagnosed NPM1-Mutated AML

By: Celeste L. Dixon
Posted: Tuesday, July 19, 2022

Based on earlier results in patients with newly diagnosed NPM1-mutated acute myeloid leukemia (AML), John C. Byrd, MD, of the University of Cincinnati College of Medicine, and colleagues are launching a global phase III trial to assess entospletinib (versus placebo) in combination with cytarabine plus daunorubicin or idarubicin induction (7 + 3) and age-adjusted high-dose cytarabine consolidation. They outlined the accruing trial in a poster presented during the European Hematology Association (EHA) 2022 Congress (Abstract P525).

Entospletinib is an oral, selective inhibitor of spleen tyrosine kinase. This kinase, the authors explained, “is a component of both lymphoid and myeloid cell signaling pathways and is implicated in the pathogenesis of a subset of AML defined by dysregulated expression of HOXA9 and MEIS1 transcription factors.” The outcome of a previous phase II study showed that induction with entospletinib plus cytarabine and daunorubicin (7 + 3) led to higher rates of complete response or complete response with incomplete hematologic recovery in patients with mutations of the NPM1 gene, compared with patients with no such mutation. NPM1 mutations have been associated with aberrant expression of HOXA9 and MEIS1.

The estimated 180 trial participants, all candidates for intensive induction, will be randomly assigned on a 1:1 basis to receive placebo or entospletinib. Thus far, the agent has been acceptably tolerated, stated the team. Patients with co-mutated FLT3 will be excluded. “The primary endpoint is the rate of measurable residual disease–negative complete response,” noted Dr. Byrd and co-investigators. “A key secondary endpoint is event-free survival.”

All patients will be followed for relapse and survival. Outcomes based on patient age (< 60 vs. ≥ 60 years) and the anthracycline administered during induction (daunorubicin vs. idarubicin) will also be examined.

Disclosure: For full disclosures of the study authors, visit

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