Aptose and NCI Partner to Advance Tuspetinib in AML and MDS Trials
Key Insights
Aptose Biosciences (search) and the National Cancer Institute (NCI) have entered a CRADA to develop tuspetinib for AML (search) and MDS (search).
Tuspetinib will be evaluated in NCI's myeloMATCH trials, focusing on targeted drug combinations for molecularly defined AML (search) and MDS (search).
Aptose is also developing tuspetinib in a triple combination therapy for newly diagnosed AML (search) patients unfit for chemotherapy.
Aptose Biosciences (search) Inc. and the National Cancer Institute (NCI) are collaborating to advance the clinical development of tuspetinib, a key drug in Aptose's pipeline, for the treatment of acute myeloid leukemia (AML (search)) and myelodysplastic syndromes (MDS (search)). The collaboration is formalized through a Cooperative Research and Development Agreement (CRADA).
Tuspetinib in myeloMATCH Trials
Under the CRADA, tuspetinib will be evaluated within the NCI's Cancer Therapy Evaluation Program (CTEP) sponsored myeloMATCH trials. These trials aim to identify effective, tailored drug combinations for AML (search) and MDS (search) patients based on the molecular profiles of their diseases. The myeloMATCH trials (NCT05564390) officially launched on May 16, 2024, and are designed to expedite the development of precision medicine approaches in treating these aggressive hematologic malignancies.
William G. Rice, Ph.D., Chairman, President and Chief Executive Officer of Aptose, stated, “The executed CRADA will facilitate our collaboration with NCI on clinical studies of novel-novel combinations with early phase II signal finding endpoints in AML (search) and MDS (search). Tuspetinib will provide the NCI and AML/MDS patients with an investigational agent that can be used to treat a broad spectrum of AML/MDS populations, including those among the most genetically challenging.”
Triple Combination Therapy: TUS+VEN+AZA
Aptose is also independently pursuing the development of tuspetinib as part of a triple drug combination with venetoclax and azacitidine (TUS+VEN+AZA) for newly diagnosed AML (search) patients who are not candidates for chemotherapy. The planned starting dose for tuspetinib in this regimen is 40 mg, a dose previously shown to be active as a single agent in relapsed or refractory AML patients. Dose escalation will be considered following safety reviews. The protocol for the Phase 1/2 TUSCANY study of TUS+VEN+AZA has been submitted to sites and reviewed by the FDA, with the study expected to commence in the fourth quarter.
Tuspetinib: A Kinase Inhibitor
Tuspetinib is an oral kinase inhibitor targeting SYK (search), FLT3 (search) (both mutated and wild type forms), KIT (search), JAK1/2 (search), and RSK2 (search) kinases. In the APTIVATE Phase 1/2 trial, tuspetinib demonstrated broad activity in AML (search) patients with diverse genetic profiles, both as a single agent and in combination with venetoclax. Responses were observed in patients with prior exposure to venetoclax, FLT3 inhibitors, and hematopoietic stem cell transplantation (HSCT), as well as in those with adverse genetic mutations such as TP53 and RAS.