Kronos Bio got the FDA sign-off to use a new primary endpoint in a leukemia trial, one that could speed up the development of its drug for a genetically defined type of acute myeloid leukemia (AML)
The company is developing the treatment, entospletinib, for patients with AML whose cancer has NPM1 mutations—that’s about 30% of adults with AML. In its upcoming phase 3 study, Kronos will measure the drug’s efficacy using a measure called minimal residual disease-negative complete response—the first time it will be used as a primary endpoint in an AML trial, said Kronos CEO Nobert Bischofberger, Ph.D., in a statement on Thursday.
Minimal residual disease, or MRD, refers to cancerous cells that can be detected in a patient after treatment, even if the drug has banished enough of their leukemia that the patient has met the criteria for a complete response. Over time, these lurking cancer cells can become active, multiply and eventually lead to a relapse.Achieving MRD negativity means that the treatment has reduced those cancer cells to levels that can’t be detected by the most sensitive sequencing tests and is linked to longer remission and survival.
Leukemia trials typically measure drug efficacy in multiple ways, from complete response rate—the proportion of patients whose cancer disappears in response to treatment—to how long the treatment helps patients live and how long it staves off relapse.
Kronos plans to start the phase 3 study of entospletinib in mid-2021. It will test the drug against placebo, both in combination with chemotherapy, in 180 adults with newly diagnosed, NPM1-mutated AML. The study will use the mutated NPM1 gene itself as a biomarker to track leukemic cells that linger in the body after treatment.
“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. In the case of NPM1-mutated AML, the mutated gene itself provides that unique marker,” said John Byrd, M.D., the D. Warren Brown Chair of Leukemia Research and Distinguished University Professor at The Ohio State University Comprehensive Cancer Center, in the statement.
The phase 3 study will also measure event-free survival, or how long entospletinib can stave off relapse and other complications. Kronos expects it to read out in the second half of 2023.
Kronos vaulted into clinical development last July, when it picked up entospletinib and a clutch of other spleen tyrosine kinase (SYK) inhibitors from Gilead. It’s a portfolio that Bischofberger knows well from his days as Gilead’s chief scientific officer.