Aptose Biosciences reported promising early results from its Phase 1/2 TUSCANY trial, testing a triplet therapy of tuspetinib, venetoclax, and azacitidine (TUS+VEN+AZA) in newly diagnosed acute myeloid leukemia (AML) patients ineligible for standard induction chemotherapy. Early data from the first cohort receiving the lowest dose of tuspetinib (40mg) shows positive clinical safety and anti-leukemic activity. Of the four patients dosed, three with FLT3-WT completed Cycle 1 with no dose-limiting toxicities or adjustments, and two achieved complete remissions.
These early findings hold significant potential for AML patients, especially those unfit for intensive chemotherapy. The achievement of complete remission in a patient with TP53 mutation, a particularly aggressive form of AML, using a less toxic regimen, is a major advancement. This suggests the triplet therapy could offer a valuable new option for this challenging patient subgroup. Additionally, the promising results in FLT3-WT patients expand the potential reach of this treatment approach to a broader population.
The data reveals that the TUS+VEN+AZA triplet was well-tolerated at the initial dose, with no observed PK interactions affecting tuspetinib levels. This allows for predictable dosing using standard venetoclax and azacitidine regimens, simplifying treatment administration. Two of the three FLT3-WT patients achieved complete remission (CR and CRh) after just one cycle, and a third patient with biallelic TP53 mutations and a complex karyotype also achieved CR. A fourth patient, with FLT3-ITD and NPM1 mutations, is currently in Cycle 1 and awaiting evaluation.
The early TUSCANY trial results suggest that TUS+VEN+AZA could become a crucial frontline therapy for a wider range of AML patients, including those with difficult-to-treat mutations, who cannot tolerate intensive chemotherapy. Continued positive data from the TUSCANY trial could reshape the treatment landscape for newly diagnosed AML, providing a safer and highly effective option for diverse patient populations.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
