Phase III trial of entospletinib is first to evaluate MRD-negative CR as primary endpoint in AML setting

A phase III trial investigating the safety and efficacy of entospletinib for the treatment of patients with newly diagnosed NPM1-mutated acute myeloid leukemia (AML) has been initiated. This trial represents the first in the AML setting to evaluate measurable residual disease (MRD)-negative complete remission (CR) as a primary endpoint.

The trial will recruit approximately 180 adult patients, who will be randomized to receive ≥2 cycles of either entospletinib or placebo, plus conventional induction and consolidation chemotherapy. The primary endpoint is MRD-negative CR, determined using next-generation sequencing (NGS).

Entospletinib is an inhibitor of the oncogene spleen tyrosine kinase (SYK), a key mediator of AML maintenance and progression via the elevated expression of HOXA9 and MEIS1 transcription factors. Aberrations in NPM1 and other AML driver genes have been associated with increased expression of these transcription factors.

In a phase Ib/II trial (NCT02343939), entospletinib in combination with intensive chemotherapy induced higher response rates in patients with NPM1-mutated AML (n = 15; 87%) compared with the entire patient population (n = 53; 70%), and was well tolerated.²  

The phase III trial is due to commence mid-2021 and the MRD data anticipated in 2023. For more information on the value of MRD status as a predictor of outcome in patients with NPM1-mutated AML, click here.