Aptose Biosciences Inc. (NASDAQ: APTO, TSX: APS) has announced a significant milestone in its quest to improve frontline therapy for newly diagnosed acute myeloid leukemia (AML) patients. The company has dosed the first set of patients in the TUSCANY Phase 1/2 study with tuspetinib (TUS) in combination with venetoclax (VEN) and azacitidine (AZA) as a frontline triple drug combination (triplet) therapy. This marks a crucial step in the development of an improved frontline therapy for AML that is active across diverse AML populations, durable, and well-tolerated.

The TUSCANY trial aims to test various doses and schedules of tuspetinib in combination with standard dosing of azacitidine and venetoclax for patients with AML who are ineligible to receive induction chemotherapy. Tuspetinib will be administered in 28-day cycles, beginning at 40mg once daily, with dose escalations planned after a safety review of each dose level. Multiple U.S. sites are enrolling in the TUSCANY trial, with anticipated enrollment of 18-24 patients by mid-late 2025.

Tuspetinib, a convenient once daily oral agent, has demonstrated broad activity across diverse AML populations in previous clinical trials. In the APTIVATE Phase 1/2 trial, tuspetinib as a single agent and in combination with venetoclax showed favorable safety and broad activity in diverse relapsed or refractory (R/R) AML populations. Responses to tuspetinib were observed in patients with prior-VEN and prior-FLT3 inhibitor (FLT3i) therapies, those with highly adverse TP53 and RAS mutations, and those with mutated or unmutated (wildtype) FLT3 genes. Tuspetinib's broad activity and favorable safety profile make it an ideal agent for frontline therapy in newly diagnosed AML patients.

The TUS+VEN+AZA triplet therapy holds the promise of delivering high response rates and longer survival to newly diagnosed AML patients while avoiding toxicities seen with other agents. This could potentially broaden the application of triplet therapy to more AML patients, including those with adverse disease features. The TUSCANY trial is designed to test this hypothesis and provide valuable data on the efficacy and safety of tuspetinib in combination with venetoclax and azacitidine.

In conclusion, Aptose's dosing of the first set of patients in the TUSCANY Phase 1/2 study marks a significant step forward in the development of an improved frontline therapy for newly diagnosed AML patients. Tuspetinib's broad activity and favorable safety profile make it an ideal agent for frontline therapy, and the TUS+VEN+AZA triplet therapy has the potential to deliver high response rates and longer survival while minimizing toxicities. The TUSCANY trial is expected to provide valuable data on the efficacy and safety of tuspetinib in combination with venetoclax and azacitidine, potentially paving the way for a new standard of care in AML therapy.