Aptose releases tuspetinib triple drug therapy data

Executive Summary

• Aptose Biosciences presented Phase 1/2 data on its triple‑drug regimen (tuspetinib + venetoclax + azacitidine) at the 67th ASH Annual Meeting, showing high response rates across all dose levels and AML sub‑populations.
• Overall complete remission (CR/CRh) rate was 90 % across 40 mg, 80 mg and 120 mg cohorts, reaching 100 % in the 80 mg and 120 mg groups, including patients with adverse FLT3‑WT, FLT3‑ITD, NPM1c, TP53/complex karyotype, RAS and MDS‑related mutations.
• The regimen was well tolerated with no dose‑limiting toxicities (DLTs), no drug‑related deaths, and 78 % MRD‑negative responses among responders; two patients proceeded to stem‑cell transplantation and remain on maintenance therapy.

Key Details

• Study Design: Ongoing Tuscan Phase 1/2 trial evaluating tuspetinib at 40 mg, 80 mg, 120 mg (and newly enrolled 160 mg) combined with standard venetoclax + azacitidine in newly diagnosed AML patients ineligible for induction chemotherapy.
• Efficacy – Overall Responses:
• CR/CRh observed in 90 % of evaluable subjects across all three dose levels.
• 100 % CR/CRh at the 80 mg and 120 mg cohorts (10/10 patients).
• Responses achieved across FLT3‑WT, FLT3‑ITD, NPM1c, TP53/complex karyotype, RAS, and MDS‑related mutation sub‑groups.
• MRD Negativity: 78 % of responding subjects were MRD‑negative by central flow cytometry.
• Safety/Tolerability:
• No dose‑limiting toxicities reported at any evaluated dose level.
• No prolonged myelosuppression in Cycle 1, no drug‑related deaths, differentiation syndrome, QTc prolongation, or CPK elevation.
• Febrile neutropenia occurred in 2 of 12 subjects (16.7 %); only one case was attributed to tuspetinib.
• 8/10 evaluable patients achieved red‑cell and platelet transfusion independence >8 weeks post‑best response.
• Transplant Outcomes: Two subjects transitioned to allogeneic stem‑cell transplantation and have returned for maintenance therapy with the triple regimen.
• Preliminary 160 mg Cohort: Early data (not included in poster) indicate rapid blast clearance, MRD negativity, and formal responses within the first few weeks of treatment.
• Quote from Dr. Rafael Bejar (CMO): “Tuspetinib, as part of a triple drug therapy, continues to perform well, achieving 100‑percent clinical response in the two higher doses we have evaluated to date… With no dose‑limiting toxicities and activity across diverse mutations, TUS+VEN+AZA targets AML’s greatest unmet needs and largest populations.”

Notable Quotes

• “We recently commenced treating patients at the highest dose level of 160 mg TUS and have already achieved early responses.” – Dr. Rafael Bejar, MD, PhD, Chief Medical Officer, Aptose Biosciences.