FDA Grants Fast Track Designation to HM432939 for Relapsed/Refractory AML

Based on results from an ongoing phase 1/2 trial, the FDA has granted fast track designation to HM432939 for patients with FLT3-mutant relapsed/refractory acute myeloid leukemia.

The FDA has granted fast track designation to HM43239 for the treatment of patients with relapsed/refractory acute myeloid leukemia (AML) with a FLT3 mutation, according to a press release from Aptose Biosciences.1

This is based upon results from an ongoing phase 1/2 trial (NCT03850574) in which the drug induced complete remissions (CRs) and was well tolerated. Previously in 2018, HM43239 received orphan drug designation for relapsed/refractory AML.

“Fast Track status acknowledges HM43239’s potential to fill an unmet need for [patients with] AML and supports our efforts as we advance it towards a potential registration study,” William G. Rice, PhD, chairman, president, and chief executive officer at Aptose Biosciences, said in the press release. “HM43239, which potently inhibits all tested forms of FLT3 and the SYK and JAK driven pathways already has delivered [CRs] in a broad diversity of relapsed or refractory AML patients in an ongoing Phase 1/2 clinical trial, including patients with prior failure of other FLT3 inhibitor agents. Fast Track designation will help facilitate the drug’s development.”

The study’s estimated enrollment was 120 patients, who received daily continuous dosing with HM43239 following enrollment. The primary end points included number of patients with a dose-limiting toxicity, area under the concentration-time curve, and maximum serum concentration. Secondary end points included best response rate via modified International Working Group criteria, duration of response, overall survival, event-free survival, and cumulative incidence or relapse.

Patients were eligible for treatment if they were 18 years or older; refractory to at least 1 cycle of prior therapy or relapsed after achieving remission with prior therapy; had an ECOG performance status of 2 or less; and had a minimum life expectancy of 3 months or more.

At the 2021 American Society of Hematology Annual Meeting & Exposition, findings from the study indicated that 13 patients were being treated in the dose-escalation cohort at a dose of 20 mg to 160 mg of treatment, and 15 patients in the dose-expansion cohort received 80 mg of treatment.2

In terms of best responses based on the International Working Group criteria, 4 patients had a CR, and 1 patient had a CR with incomplete count recovery. All 5 patients who achieved a composite CR (CRc) were treated at the 80 mg dose. The CRc rate at the 80 mg dose was 26.3%. Of the 8 patients whohad a FLT3 mutation and were treated at the 80 mg dose, 3 patients achieved CRc. Among patients who were FLT3 wild-type (n = 11), CRc were achieved in 2. Moreover, of the remaining 4 patients with CRc, 3 went on to receive a hematopoietic stem cell transplant and were alive and in remission at the time of the presentation.

Treatment-emergent adverse effects were observed with diarrhea (14%), nausea (7%), vomiting (7%), and alanine aminotransferase increase (7%), with no patients having events that were higher than grade 3.


  1. Aptose receives fast track designation for HM43239 in relapsed/refractory AML patients and FLT3 mutation. News release. Aptose Biosciences Inc. May 4, 2022. Accessed May 5, 2022. https://bit.ly/3LO4oOc
  2. Daver NG, Lee KH, Yoon S-S, et al. HM43239, a novel potent small molecule FLT3 inhibitor, in acute myeloid leukemia (AML) with FMS-like Tyrosine Kinase 3 (FLT3) mutations: phase 1/2 study. Blood. 2019;134(suppl 1):1331. doi:10.1182/blood-2019-129670
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