Study of Tuspetinib Moves to Expand the Population of Patients With FLT3+ AML


The novel FLT3 inhibitor, tuspetinib, will be investigated further in patients with FLT3-positive acute myeloid leukemia.

Tuspetinib (formerly HM43239) will undergo further evaluation for the treatment of patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) as part of a phase 1/2 expansion trial (APTIVATE; NCT03850574).1

Tuspetinib is a novel FLT3 inhibitor that simultaneously targets SYK, JAK1/2, FLT3, and other kinases in AML. In preclinical cell lines, the agent showed therapeutic efficacy for the treatment of AML, and signaled potential to help overcome resistance to therapies and prevent AML relapse.2

“We are pleased to have dosing underway in our APTIVATE clinical trial of tuspetinib in a very ill R/R AML population,” said William G. Rice, PhD, chairman, president, and Chief executive officer, Aptose Biosciences, in a press release.1 “Tuspetinib has demonstrated noteworthy safety and mutation agnostic potency across a spectrum of AML patients with a diversity of adverse mutations, further distinguishing it from competing compounds and targeting a much larger AML population. This breadth of activity along with its significant safety profile has allowed us to define a precise clinical and commercial plan for tuspetinib in multiple lines of therapy, including its use in doublet and triplet combinations, as well as maintenance therapy.”

In the prior dose-escalation phase, treatment with tuspetinib administered at 80 mg, 120 mg, and 160 mg led to composite complete remissions (CRc) in patients and was well-tolerated. There were no dose-limiting toxicities observed with the agent, nor where there any serious adverse events (SAEs).

Fifty patients with AML were included in the dose-escalation phase. Of the 22 patients with FLT3-mutated AML, 18% achieved clinical response, including 4 patients with a CRc and 1 partial response (PR). Patients previously treated with gilteritinib (Xospata) and/or midostaurin (Rydapt) also achieved clinical responses with tuspetinib. Specifically, there were 2 patients a CRc and 1 patient with a PR.

Responses by FLT3-mutant AML subtype were also highlighted in the results. Among patients with FLT3-positive disease, the response rate was 8%. Patients with FLT3 wild-type had a response rate of 19%, and those with FLT3-positive disease who received a prior FLT3 inhibitor had a response rate of 27.3%. Patients who were both FLT3-positive and NPM1-positive had a response rate of 66.7%, and those who were FLT3-positive, NPM1-positive, and had DNMT3A-altered tumors had a 75% response rate. Finally, the subgroup of patients with natural killer-RAS tumors had a response rate of 37.5%.

In the open-label, multicenter, dose escalation portion of the APTIVATE study, up to 218 patients with FLT3-mutated AML will be enrolled. Patients are required to have morphologically documented primary or secondary AML by the World Health Organization criteria, an ECOG performance status of 2 or lower, and adequate laboratory values at the time of screening.3

The study will primarily evaluate the safety and tolerability of tuspetinib. The secondary end points of the study include anti-leukemic activity, pharmacokinetics, and pharmacodynamics.

Three sites in the United States are actively recruiting patients for this study. There are also several study sites in the Republic of Korea.


1. Aptose initiates dosing of tuspetinib in APTIVATE Expansion trial in patients with acute myeloid leukemia. News release. Aptose Biosciences. January 30, 2023. Accessed January 30, 2023.

2. Lee M. Ha YE, Moon MJ, et al. Abstract 804: Antitumor activity of the potent and novel FLT3 inhibitor HM43239 in acute myeloid leukemia. Cancer Res. 2018;78 (suppl 13): 804. doi:10.1158/1538-7445.AM2018-804

3. Daver N, Lee KH, Jonas BA, et al. A phase 1/2 dose escalation study of the myeloid kinase inhibitor hm43239 in patients with relapsed or refractory acute myeloid leukemia. Blood. 2022; 140 (suppl 1): 6197–6199. doi:10.1182/blood-2022-167972

Related Videos
Related Content