Entospletinib in combination with chemotherapy will be evaluated in the phase 3 AGILITY study in patients with NPM1-mutated AML.
The first patient has been dosed in the phase 3 AGILITY study of entospletinib in patients with newly diagnosed NPM1-mutated acute myeloid leukemia (AML), according to a press release by Kronos Bio, Inc.
Entospletinib is a selective inhibitor targeting spleen tyrosine kinase. The agent is designed for the frontline treatment of NPM1-mutated AML. The agent has been investigated in over 700 patients with a variety of hematological malignancies. Clinical activity has been seen in patients with AML who have NPM1 mutations and MLL rearrangements.
“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, PhD, president and chief executive officer of Kronos Bio, in a press release. “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.”
The phase 3 study (NCT05020665) has a target enrollment of 180 participants and an estimated study completion date of December 2026. The primary end point is measurable residual disease negative complete response rate. Secondary end points include event-free survival, relapse-free survival, overall survival, complete response rate, and the number of participants who experience a treatment-emergent adverse event.
During the study, patients will be randomized 1:1 into either the experimental or the control arm. Patients in the experimental arm will receive a combination of intensive chemotherapy and entospletinib. Patients in the control arm will receive intensive chemotherapy and a matching placebo. Patients may receive up to 5 cycles.
In order to participate in the study, patients must be between 18 and 75 years of age, have a previously untreated de novo AML, AML with myelodysplastic syndromes features, or therapy-related AML, NPM1-mutated disease, an ECOG performance status of 0, 1, or 2, and adequate hepatic and renal function.
Patients with isolated myeloid sarcoma, known central nervous system involvement with leukemia, active infection with hepatitis B, C, or known HIV, active COVID-19 either symptomatic or asymptomatic, disseminated intravascular coagulation with active bleeding or signs of thrombosis, a history of prior allogeneic hematopoietic stem cell transplant or solid organ transplant, treatment with pump inhibitors 7 days prior to enrollment until 48 hours after completion of entospletinib or placebo, ongoing immunosuppressive therapy, clinical signs or symptoms of leukostatis, clinically significant heart disease, an ongoing infection, or are unable to swallow tablets are not eligible to participate.
“We are pleased to be participating in this trial, with the goal of improving outcomes for patients with AML,” said Karamjeet S. Sandhu, MD, assistant professor in the Department of Hematology and Hematopoietic Cell Transplantation at City of Hope, in a press release. “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.”
Currently, the study is recruiting in California, New York, and South Carolina.