Kronos Bio, Inc. (Nasdaq: KRON), a company dedicated to transforming the lives of those affected by cancer, today announced that the first patient has been dosed in a Phase 1b/2 clinical trial of lanraplenib in combination with gilteritinib in patients with relapsed/refractory FLT3-mutated acute myeloid leukemia (AML).
Lanraplenib is the company’s next-generation spleen tyrosine kinase (SYK) inhibitor. In addition to lanraplenib, Kronos Bio is also evaluating its lead investigational SYK inhibitor, entospletinib, in the Phase 3 registrational AGILITY study as a treatment for newly diagnosed patients with NPM1-mutated AML in combination with standard induction and consolidation chemotherapy. While entospletinib and lanraplenib have equivalent preclinical anti-leukemic activity and selectivity for SYK, lanraplenib’s pharmacologic properties may be advantageous in regimens that are dosed to progression, such as the investigational gilteritinib combination.
The Phase 1b/2 lanraplenib clinical trial is a multi-center, open-label, dose-escalation study enrolling patients with relapsed/refractory FLT3-mutated AML. This trial is being conducted in two stages: a dose-escalation stage and an expansion stage. The first stage is evaluating initial safety, pharmacokinetic and anti-leukemic activity of escalating once-daily doses of lanraplenib in combination with the standard approved dose of gilteritinib. This stage also will assess FLT3 measurable residual disease (MRD) negative rate in patients who achieve a complete response (CR) and explore the predictive value of a number of biomarkers that may correlate with clinical outcomes.
Once a recommended dose is established, an expansion stage is planned to further evaluate the safety of lanraplenib and assess its anti-leukemic activity as measured by CR rate and duration of response.
“The initiation of this study is an important first step as we advance lanraplenib for patients with certain genetically defined types of AML,” said Jorge DiMartino, M.D., Ph.D., chief medical officer and executive vice president of Clinical Development at Kronos Bio. “Our long-term vision is to develop lanraplenib as a cornerstone of targeted regimens for these patients, allowing us to potentially reach as many as two-thirds of patients with AML. Today’s announcement represents important progress toward that goal.”
Kronos Bio currently has three investigational compounds in clinical development. In addition to the SYK inhibitors, which were acquired from Gilead Sciences, Inc., the company is advancing KB-0742, a highly selective, orally bioavailable inhibitor of cyclin dependent kinase 9 (CDK9) as a treatment for MYC-amplified solid tumors. KB-0742 is currently being studied in a Phase 1/2 trial and is the first compound discovered through the company’s proprietary small molecule microarray (SMM) screening platform.
Learn more about Krono Bio’s clinical trials here.