Aptose's Tuspetinib Exceeds Expectations When Combined with Standard of Care Treatment Across Diverse Populations of Newly Diagnosed AML
Executive Summary
- Phase 1/2 “TUSCANY” trial of tuspetinib (TUS) + venetoclax (VEN) + azacitidine (AZA) in newly diagnosed AML shows 90% overall CR/CRh rate (9/10 patients).
- MRD‑negativity achieved in 78% of responding patients (7/9); responses observed across all major mutational subtypes, including TP53‑mutated and FLT3‑ITD disease.
- Safety profile remains favorable with no dose‑limiting toxicities, differentiation syndrome, QTc prolongation, prolonged myelosuppression, CPK elevation, or treatment‑related deaths; dosing now escalated to 160 mg TUS.
Key Details
- Efficacy:
- CR/CRh in 6/6 (100%) patients at 80 mg and 120 mg dose levels – exceeds the ~66% expected from VEN+AZA alone.
- Overall CR/CRh: 9/10 (90%).
- FLT3‑wildtype AML: 7/8 (88%) CR/CRh, representing ~70% of AML population.
- MRD‑negativity by central flow cytometry in 7/9 (78%) responding patients.
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Responses observed in all tested mutational subtypes: unmutated FLT3, FLT3‑ITD, NPM1c, biallelic TP53 with complex karyotype, RAS, and myelodysplasia‑related mutations.
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Safety:
- No dose‑limiting toxicities (DLTs) reported to date.
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No treatment‑related deaths, differentiation syndrome, QTc prolongation, prolonged myelosuppression in Cycle 1 remission, or CPK elevations at any dose level.
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Dosing & Enrollment:
- Dosing initiated at 40 mg, escalated through 80 mg and 120 mg cohorts; now ongoing at 160 mg TUS.
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Trial conducted at 10 U.S. sites with planned enrollment of 18‑24 patients by end‑2025.
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Presentation:
- Data presented as a poster at the European School of Haematology (ESH) 7th International Conference on Acute Myeloid Leukemia, Oct 16‑18, 2025, Estoril, Portugal.
Notable Quotes
“We have observed that TUS can be safely added to a backbone VEN+AZA without needing to reduce the dose of these standard‑of‑care drugs… The activity we have observed with the TUS triplet in the first 10 patients has exceeded our expectations with 9 achieving complete remissions and 7 demonstrating MRD‑negativity…” – Rafael Bejar, M.D., Ph.D., Chief Medical Officer, Aptose Biosciences.