Aptose's Triple Therapy Shows Promising Results in New AML Patients in TUSCANY Trial

Aptose Biosciences Inc., a clinical-stage precision oncology company, recently announced encouraging preliminary safety and response data from their Phase 1/2 TUSCANY trial. This study involves administering a 40 mg dose of tuspetinib in tandem with standard doses of venetoclax and azacitidine, collectively known as the TUS+VEN+AZA triplet, to patients newly diagnosed with acute myeloid leukemia (AML). This triplet therapy is under development as a primary treatment option for AML patients who are unable to undergo induction chemotherapy, addressing a broad and genetically varied patient population.

The TUSCANY trial was initiated in January 2025, marking the beginning of treatment in the first cohort of newly diagnosed AML patients with the lowest initial dose of tuspetinib as part of the TUS+VEN+AZA combination. The early findings from this trial indicate promising safety and anti-leukemic effects.

Currently, four patients have been treated with the 40 mg tuspetinib dose as part of the combination therapy. Among them, three patients with unmutated FLT3 genes successfully completed the first treatment cycle without experiencing any dose-limiting toxicities or requiring dose modifications. Impressively, two of these patients achieved complete remission by the end of the first cycle. Additionally, a patient with biallelic TP53 mutations and a complex karyotype also achieved complete remission. Another patient with unmutated FLT3 showed substantial reductions in bone marrow leukemic blasts and is continuing therapy in the second cycle. The fourth patient, possessing both FLT3-ITD and NPM1 mutations, is currently undergoing treatment in the first cycle and has not yet reached the response evaluation phase.

Pharmacokinetic studies have shown that the plasma levels of tuspetinib remain stable with the addition of azacitidine, ensuring predictability and avoiding the need for dose adjustments due to pharmacokinetic interactions. The trial's Chief Medical Officer, Dr. Rafael Bejar, noted that these initial results are promising, highlighting the achievement of complete remission in Cycle 1 for a patient with a TP53 mutation, which is typically associated with a poor prognosis in AML. As the trial progresses and enrollment continues, further data will be released.

Dr. William G. Rice, Chairman, President, and CEO of Aptose, emphasized the potential of the TUS+VEN+AZA therapy to treat a wide range of AML patients, including those with difficult-to-treat mutations, from the start of treatment. The therapy’s ability to maintain a favorable safety profile without altering the standard dosing regimen sets it apart from other AML treatments in development.

The TUSCANY trial aims to refine and advance the TUS+VEN+AZA triplet therapy as an effective and durable frontline treatment for AML patients. This involves testing various doses and schedules of tuspetinib in combination with standard doses of azacitidine and venetoclax, particularly for patients who cannot receive induction chemotherapy. Tuspetinib is administered orally once daily in 28-day cycles, starting at 40 mg per day, with plans for dose escalation following safety reviews. The trial is anticipated to enroll 18-24 patients by mid to late 2025, with multiple U.S. sites participating.

Aptose Biosciences is committed to developing precision medicines for oncology, focusing initially on hematology. Their lead clinical-stage oral kinase inhibitor, tuspetinib, has shown promising activity both as a standalone treatment and in combination therapies for patients with relapsed or refractory AML. The company is working to establish tuspetinib as a frontline triplet therapy for newly diagnosed AML.