Aptose reports 86% response rate in AML triplet therapy trial at EHA
Aptose Biosciences presented updated clinical data from its TUSCANY Phase 1/2 study at the European Hematology Association Congress in Stockholm this week, reporting an 86.2% composite complete response rate across 29 evaluable patients treated with its tuspetinib (TUS) triplet regimen in newly diagnosed acute myeloid leukaemia.
The trial is evaluating TUS in combination with the standard-of-care doublet of venetoclax and azacitidine (VEN+AZA) in patients ineligible for induction chemotherapy. Thirty-two patients in total have been dosed across four cohorts: 40 mg, 80 mg, 120 mg, and 160 mg of TUS. Among patients who achieved a complete or complete-with-partial-haematological-recovery response, 86.4% also achieved minimal residual disease (MRD) negativity, a marker associated with durable remission.
Efficacy and safety highlights
At the highest dose level of 160 mg (n=13), the composite complete response rate was 76.9%, including all four patients harbouring TP53 mutations with complex karyotype, a subgroup historically associated with very poor outcomes on existing regimens. The company described TUS as "mutation agnostic," pointing to responses across unmutated FLT3, TP53-mutant, and complex karyotype presentations. Nineteen patients remain on treatment and six have proceeded to stem cell transplantation, suggesting durable disease control in a proportion of the cohort.
On safety, Aptose reported no treatment-related deaths and no events of QTc prolongation, creatine phosphokinase elevations, or differentiation syndrome. The company also noted that the pharmacokinetic profile of TUS was not materially altered by co-administration with venetoclax, azacitidine, antifungals, or food, which is a practically important finding for a once-daily oral agent used in an older, medically complex patient population.
Rafael Bejar, Chief Medical Officer at Aptose, said the triplet "is a first line combination therapy with the potential to improve outcomes in nearly all AML populations," though he acknowledged the programme is still in Phase 1/2 dose-finding and these remain early results. The oral presentation was delivered by Nikolai Podoltsev, Associate Professor of Medical Oncology and Hematology and Clinical Director of Malignant Hematology at Yale School of Medicine.
Market and competitive context
The newly diagnosed AML landscape for patients unfit for intensive chemotherapy has been substantially reshaped by the approval of the VEN+AZA doublet itself, which demonstrated overall survival benefit over azacitidine alone in the VIALE-A trial. Response rates in that pivotal study were in the 66% composite complete remission range, making Aptose's reported 86.2% figure notable, though cross-trial comparisons carry significant caveats given differences in patient selection, dosing schedules, and follow-up duration.
Several companies are pursuing triplet strategies to build on VEN+AZA, targeting kinases, IDH mutations, FLT3, and other drivers. The particular challenge Aptose is attempting to address is the residual unmet need in genetically adverse subgroups, particularly TP53-mutant AML, where venetoclax-based regimens have historically performed poorly. If the TP53 response signal at the 160 mg cohort holds in a larger dataset, it would be clinically meaningful, as this subgroup has few effective options.
Aptose is a small-cap company listed on the Toronto Stock Exchange and OTC markets. TUSCANY is being conducted at ten US clinical sites. The company has not disclosed a timeline for a Phase 3 decision or any partnership discussions, and investors will be watching for both a dose optimisation announcement and longer-term survival data as the primary next milestones.