Tuspetinib Triplet Combination Shows Antileukemic Activity in AML

Tuspetinib in combination with standard-of-care venetoclax and azacitidine showed promising clinical safety and antileukemic activity in patients with newly diagnosed acute myeloid leukemia (AML) who are ineligible for induction chemotherapy, according to an update of the phase 1/2 TUSCANY trial from Aptose Biosciences, Inc.

In the TUSCNAY trial, four patients in the first cohort received 40 mg of tuspetinib and three patients in the second cohort received 80 mg of tuspetinib. In the 40 mg cohort, three patients (two with FLT3-wildtype and one with both FLT3-wildtype and TP53-mutated complex karyotype) achieved measurable residual disease  negativity and either complete remission or complete remission with incomplete count recovery (CR/CRi). The fourth patient did not respond while receiving 40 mg and discontinued treatment. No dose-limiting toxicities were observed.

In the 80 mg cohort, all three patients with diverse mutation profiles achieved blast reductions and CR/CRi in the first cycle and are expected to show further improvement as they continue treatment. Eighty milligrams was determined to be the optimal tuspetinib dose.

“The treatment paradigm for AML is shifting to triplet combination therapy,” said Rafael Bejar, MD, PhD, chief medical officer of Aptose, in a press release. “We have always maintained that tuspetinib, with its notable safety profile and ability to treat the larger, difficult-to-treat AML populations with high-risk mutations, could be an ideal drug for a triplet combination therapy in the frontline setting. With the majority of patients already achieving complete responses—including early responses in patients with adverse mutations—the clinical findings to date are bearing that out.”

Reference

GlobeNewswire. Accessed May 12, 2025. https://www.globenewswire.com/news-release/2025/05/05/3073937/35575/en/Aptose-Provides-Clinical-Update-for-the-Tuspetinib-based-Triple-Drug-Frontline-Therapy-in-Newly-Diagnosed-AML-Patients-from-the-Phase-1-2-TUSCANY-Trial.html