Benzinga | Dec 6, 2021 07:11AM EST

Kronos Bio Announces First Patient Dosed In AGILITY Phase 3 Clinical Trial Of Entospletinib In Patients With Newly Diagnosed NPM1-mutated Acute Myeloid Leukemia

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 the registrational Phase 3 AGILITY clinical trial of entospletinib, a selective inhibitor targeting spleen tyrosine kinase (SYK), in combination with standard of care anthracycline and cytarabine (7+3) chemotherapy. This trial is the first in acute myeloid leukemia (AML) to use measurable residual disease (MRD) as the primary endpoint and has the potential to support accelerated approval of entospletinib by the U.S. Food and Drug Administration (FDA) as a treatment for patients newly diagnosed with NPM1-mutated AML who are fit for intensive induction.

"With the initiation of this trial, we are taking an important step forward for patients with AML, a form of blood cancer that has been difficult to treat historically," said Norbert Bischofberger, Ph.D., president and chief executive officer of Kronos Bio. "Even with current therapies, about half of people newly diagnosed with NPM1-mutated AML will die from the disease within five years. The use of the novel endpoint of MRD provides a pathway to potentially bring entospletinib to patients more quickly."

Entospletinib is Kronos Bio's lead product candidate, and the company expects to share data from the trial in the second half of 2023. The randomized, double-blind, placebo-controlled trial is designed to assess the efficacy and safety of entospletinib in combination with intensive induction and consolidation chemotherapy in approximately 180 adults who have been newly diagnosed with NPM1-mutated AML. This trial will test the hypothesis, based on robust preclinical and Phase 2 clinical data, that NPM1 mutation leads to dependency on SYK signaling. The NPM1 mutation is present in about 30% of all adult patients with AML.

"We are pleased to be participating in this trial, with the goal of improving outcomes for patients with AML," said Karamjeet S. Sandhu, M.D., assistant professor in the Department of Hematology and Hematopoietic Cell Transplantation at City of Hope, a world-renowned research and treatment organization near Los Angeles that was the first to dose a patient in the trial. "Patients with NPM1-mutated AML are in need of better treatment options, and we are excited that we are the first center to begin treating a patient in this trial."

The primary endpoint of the trial is MRD negative complete response (CR), as measured by molecular detection of mutant NPM1 alleles in bone marrow, which affords a high degree of sensitivity to detect MRD. Numerous clinical studies have shown that patients with NPM1 mutations who achieve MRD negative CR after induction chemotherapy survive longer than patients who achieve CR but have detectable MRD. If successful, this would be the first time MRD is used as the basis for seeking accelerated approval in AML.

The decision to proceed with this trial design was made after an End-of-Phase 2 discussion with the FDA. In the trial, patients will be randomized 1:1 to receive either entospletinib or placebo in combination with standard induction and consolidation chemotherapy. Remission and MRD status will be assessed after the first two cycles of chemotherapy and patients may receive up to a total of five cycles. Event-free survival (EFS) is a key secondary endpoint, and mature EFS data will potentially be used to support full approval.

Kronos Bio acquired entospletinib and another SYK inhibitor, lanraplenib, from Gilead Sciences in July 2020. As previously announced, under the agreement with Gilead, the initiation of the Phase 3 trial triggers a $29 million milestone payment from Kronos Bio to Gilead. The payment will be recorded in the fourth quarter.

Lanraplenib is being developed for the treatment of patients with relapsed/refractory FLT3-mutated AML and patients newly diagnosed with NPM1-mutated and/or FLT3-mutated AML who are older than 75 years old or are not eligible for intensive induction chemotherapy.