On February 12, 2025 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company, reported promising early safety and response results from newly diagnosed acute myeloid leukemia (AML) patients dosed in Aptose’s Phase 1/2 TUSCANY trial with a 40 mg dose of tuspetinib in combination with standard of care dosing of venetoclax and azacitidine (TUS+VEN+AZA triplet) (Press release, Aptose Biosciences, FEB 12, 2025, View Source [SID1234650207]). The TUS+VEN+AZA triplet is being developed as a frontline therapy to treat large, mutationally diverse populations of newly diagnosed AML patients who are ineligible to receive induction chemotherapy.

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In January 2025, Aptose announced the initiation of the TUSCANY trial and dosing in the first cohort of newly-diagnosed AML patients with the lowest starting dose (40 mg) of TUS as part of the TUS+VEN+AZA triplet, and the early data reveal promising clinical safety and antileukemic activity.

To date, four newly diagnosed AML patients have received the lowest dose of TUS (40 mg) as part of the (TUS+VEN+AZA) combination.
Three patients with unmutated (wildtype) FLT3 (FLT3-WT) completed Cycle 1 of treatment with no dose-limiting toxicities (DLTs) and no dose adjustments.
Two FLT3-WT patients achieved complete remissions (CR and CRh) by the end of Cycle 1.
Notably, a patient with biallelic TP53 mutations and a complex karyotype obtained CR.
The third FLT3-WT patient experienced significant reductions in bone marrow leukemic blasts during Cycle 1 and remains on therapy in Cycle 2.
The fourth patient, harboring FLT3-ITD and NPM1 mutations, is currently dosing in Cycle 1 and is not yet eligible for response evaluation
Pharmacokinetic (PK) analyses for TUS show plasma levels unaffected by the addition of AZA, providing predictability and avoiding the need for dose alterations due to PK interactions.
"These are very promising early results from the TUSCANY trial of TUS+VEN+AZA and the first indicators of the safety and efficacy we expected to see in newly diagnosed AML patients," said Rafael Bejar, M.D., Ph.D., Chief Medical Officer of Aptose. "To achieve a complete remission (CR) in Cycle 1 in a subject harboring a TP53 mutation – one of the most adverse forms of AML – is particularly encouraging. With enrollment ongoing in the TUSCANY study, we look forward to reporting additional data as it becomes available."

"TUS+VEN+AZA triplet therapy has the potential to treat large AML patient populations, including those with traditionally difficult-to-treat mutations, and improve patient outcomes right from the outset of treatment," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer of Aptose. The ability to treat such diverse AML populations – including FLT3 wildtype patients – with a favorable safety profile and without having to alter the standard of care dosing, differentiates our drug from many AML drugs in development."

TUSCANY: TUS+VEN+AZA Triplet Phase 1/2 Study
Tuspetinib based TUS+VEN+AZA triplet therapy is being advanced in the TUSCANY Phase 1/2 trial with the goal of creating an improved frontline therapy for newly diagnosed AML patients that is active across diverse AML populations, durable, and well tolerated. Earlier APTIVATE trials of TUS as a single agent and in combination as TUS+VEN demonstrated favorable safety and broad activity in diverse relapsed or refractory (R/R) AML populations that went beyond the more prognostically favorable NPM1 and IDH mutant subgroups. Responses to TUS were also observed in those 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.

The TUSCANY triplet Phase 1/2 study is designed to test various doses and schedules of TUS in combination with standard dosing of AZA and VEN for patients with AML who are ineligible to receive induction chemotherapy. A convenient, once daily oral agent, TUS 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. Data will be released as it becomes available.

More information on the TUSCANY Phase 1/2 study can be found on www.clinicaltrials.gov.