NEW YORK – Kronos Bio on Monday said it has dosed the first patient with newly diagnosed NPM1-mutated acute myeloid leukemia in the Phase III AGILITY trial, in which it is studying the activity of its SYK inhibitor entospletinib with standard-of-care chemotherapy against just chemo.
Approximately 30 percent of adult AML patients have NPM1 mutations and new therapies are needed for this subset of patients, Kronos CEO Norbert Bischofberger noted in a statement. "Even with current therapies, about half of people newly diagnosed with NPM1-mutated AML will die from the disease within five years," he said.
In the double-blind placebo-controlled AGILITY trial, researchers will randomize around 180 newly diagnosed NPM1-mutated AML patients to either entospletinib and intensive chemotherapy or just intensive chemo. The primary endpoint is minimal residual disease-negative complete response, as determined by the level of mutant NPM1 alleles in patients' bone marrow samples. "The use of the novel endpoint of MRD provides a pathway to potentially bring entospletinib to patients more quickly," Bischofberger noted.
Kronos expects data from AGILITY in the second half of 2023 and will seek accelerated approval for entospletinib plus chemo in this setting if this data is positive. If the program reaches this stage, the company believes this will be the first time MRD is used as the basis for accelerated approval in AML.
The Phase III trial exploring the activity of Kronos' SYK inhibitor is designed based on data from a Phase II study, which showed that NPM1-mutated AML is dependent on SYK signaling. A key secondary endpoint in AGILITY is event-free survival, which Kronos may use to support full approval for the treatment.
Kronos acquired entospletinib and a second SYK inhibitor lanraplenib from Gilead Sciences in July 2020. That deal stipulated a $29 million milestone payment upon the start of a Phase III trial, which Kronos will record in the fourth quarter. Kronos is developing lanraplenib as a treatment for patients with relapsed or refractory FLT3-mutated AML and newly diagnosed AML patients who are older than 75 years old, have NPM1 and/or FLT3 mutations, and can't receive intensive induction chemotherapy.