NEW YORK – Kronos Bio said on Thursday it will begin a Phase III trial of entospletinib in NPM1-mutated acute myeloid leukemia this year after positive feedback from the US Food and Drug Administration on its Phase II study.
The Phase III trial, slated to begin in mid-2021, will enroll approximately 180 newly diagnosed AML patients with NPM1 mutations who will receive either entospletinib plus chemotherapy or placebo plus chemo. As the primary endpoint of the trial, researchers will track the proportion of patients who achieve measurable residual disease (MRD)-negative complete response as assessed by next-generation sequencing.
NGS testing for MRD allows for the detection of leukemic cells that remain in the body even after a patient is deemed to be in complete response by standard clinical criteria. AML patients who are MRD negative typically have longer remissions and improved survival, said John Byrd, professor at The Ohio State University Comprehensive Cancer Center and chief medical officer of the Leukemia & Lymphoma Society's Beat AML Master Trial, in a statement.
The Phase III entospletinib study will be the first AML trial to use MRD status as a primary outcome measure, according to Kronos. "MRD has been used as a surrogate endpoint for approvals in other forms of leukemia but not for AML, in part due to the requirement for a unique marker that can be used to track rare residual leukemia cells," Byrd added. "In the case of NPM1-mutated AML, the mutated gene itself provides that unique marker."
In the Phase II trial of entospletinib plus chemo, the complete response rate was 70 percent among 53 enrolled patients.