Aptose Biosciences’ Phase 1/2 TUSCANY trial of tuspetinib (TUS) in combination with venetoclax and azacitidine (VEN/AZA) has cleared the 120mg TUS dose cohort with no dose-limiting toxicities (DLTs). The Cohort Safety Review Committee (CSRC) has endorsed escalating to the 160mg TUS dose level. The company also secured an additional US$1.1M advance from its loan agreement with Hanmi Pharmaceutical, bringing the total received to US$5.6M.
The continued dose escalation without significant safety signals reinforces the potential viability of the TUS+VEN+AZA triplet as a frontline therapy for newly diagnosed acute myeloid leukemia (AML) patients ineligible for intensive induction chemotherapy. The achievement of complete remissions (CRs) and minimal residual disease (MRD)-negativity across multiple dose cohorts further strengthens the therapy’s clinical profile. Notably, this positive response has been observed even in patients with adverse genetic markers like biallelic •TP53• or •FLT3•-ITD mutations.
Aptose is pursuing a distinct strategic path by prioritizing this triplet combination for a patient population often overlooked in AML drug development. This focus on an older, frailer demographic aligns with the increasing need for less toxic treatment options and underscores the potential market opportunity for a well-tolerated, effective regimen. Furthermore, the triplet’s observed efficacy across a range of genetic subtypes could simplify patient selection compared to more targeted approaches.
This development has several key implications for the AML treatment landscape. For clinicians, the TUS+VEN+AZA combination could offer a valuable new tool for managing patients unable to tolerate aggressive chemotherapy. For Aptose, a successful Phase 1/2 trial could pave the way for accelerated regulatory pathways and a potential first-in-class therapy. For competing sponsors, Aptose’s progress validates the continued investigation of combination approaches for this patient segment.
Looking ahead, the 160mg TUS dose cohort will be critical in determining the maximum tolerated dose and further clarifying the efficacy profile. Durability of response and long-term survival data will be essential for regulatory success. Aptose’s ability to scale up manufacturing and secure future commercial partnerships will also play a significant role in its ability to bring the TUS+VEN+AZA triplet to market. Ultimately, the trial’s outcome will shape the direction of frontline AML treatment and influence the ongoing debate regarding the role of combination therapies in this challenging disease.
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.
