Aptose releases Tuspetinib early results for AML

Executive Summary

• Aptose Biosciences reported early data from the Phase 1/2 Tuscany trial, demonstrating that tuspetinib (TUS) improves standard of care treatment (Venetoclax + Azacitidine) in newly diagnosed Acute Myeloid Leukemia (AML).
• The data supports the safety and efficacy of the TUS+VEN+AZA triplet therapy across diverse AML populations, including those with difficult-to-treat mutations (biallelic TP53, FLT3-ITD, and RAS-mutant).
• No dose-limiting toxicities (DLTs) or treatment-related deaths were observed at the completed dose levels (40 mg, 80 mg, and 120 mg), with 100% Complete Response/Complete Remission with incomplete hematologic recovery (CR/CRh) rates observed at the 80 mg and 120 mg levels.

Key Details

• Trial Status: Phase 1/2 Tuscany trial initiated in December 2024; currently evaluating TUS+VEN+AZA triplet therapy.
• Patient Cohort: Data reported from 10 patients across three dose cohorts (40 mg, 80 mg, and 120 mg TUS).
• Efficacy Metrics:
  • CR/CRh Rates: 100% CR/CRh observed in all subjects treated at 80 mg and 120 mg TUS dose levels.
  • MRD-Negativity: 78% (7 of 9) of responding patients achieved Minimal Residual Disease (MRD) negativity.
  • Specific Mutations: 100% CR/CRh and 100% MRD-negativity observed in five patients with biallelic TP53-mutant, FLT3-ITD, and RAS-mutant AML.
  • Response Speed: Trend toward achieving Complete Remissions (CRs) more quickly at higher dose levels (120 mg vs. 40 mg/80 mg).
  • Durability: No loss of MRD-negativity observed to date; no relapses reported; one patient maintained MRD-negativity for over seven months.
• Safety Profile:
  • No significant safety concerns or dose-limiting toxicities (DLTs) observed at 40 mg, 80 mg, or 120 mg doses.
  • No prolonged myelosuppression in cycle 1 for subjects in remission.
  • No reports of drug-related QTc prolongation or differentiation syndrome (DS).
  • No treatment-related deaths.
  • Nine out of 10 dosed patients remain on study.
• Next Steps: Enrollment is advancing to the 160 mg TUS dose level following a cohort safety review committee (CSRC) meeting.
• Trial Design:
  • Objective: Develop a safe, well-tolerated, mutation-agnostic front-line therapy for newly diagnosed AML patients ineligible for induction chemotherapy.
  • Sites: 10 leading United States clinical sites.
  • Dosing: Once-daily oral TUS in 28-day cycles combined with standard dosing of Azacitidine (AZA) and Venetoclax (VEN).
  • Enrollment Target: Anticipated enrollment of 18 to 24 patients by late 2025.
• Non-Responder: The only non-responder was a patient at the initial 40 mg dose level who did not achieve TUS exposures previously associated with response.

Notable Quotes

• William G. Rice, PhD, Chairman, President and CEO: "We already have data from three different TUS dose levels in the Tuscany trial, and the data continue to strengthen at higher doses of TUS and over time. We are building a strong case for TUS+VEN+AZA as a triplet front-line therapy of choice to address a broad AML population, including subgroups with the most adverse of mutations."
• Rafael Bejar, MD, PhD, Chief Medical Officer: "As illustrated in the data highlights, the addition of TUS to VEN+AZA appears to boost response rates and MRD-negativity while maintaining favourable safety and tolerability... And the 100 per cent CR/CRh and 100 per cent MRD-negativity rates among the five biallelic TP53-mutant, FLT3-ITD and RAS-mutant AML cases are exciting to see, as this can correlate with longer overall survival."