The following is a summary of “Phase I study evaluating the Fc-optimized FLT3 antibody FLYSYN in AML patients with measurable residual disease,” published in the August 2023 issue of Hematology by Heitmann et al.
AML patients (50%) attain complete remission (CR), exhibit measurable residual disease (MRD), and subsequently experience relapse. FLYSYN, a specially engineered antibody targeting FLT3/CD135, is highly present in AML cells. Researchers performed a retrospective study to develop and evaluate the efficacy and safety of FLYSYN, an Fc-optimized antibody for eradicating MRD in AML patients who have achieved CR.
They conducted a first-in-human, open-label, single-arm, multicenter trial involving AML patients with persistent or increasing MRD in CR. This accessed FLYSYN’s safety, pharmacokinetics, and preliminary efficacy across distinct intravenous doses (cohorts 1–5: 0.5 mg/m2, 1.5 mg/m2, 5 mg/m2, 15 mg/m2, 45 mg/m2; cohort 6: 15 mg/m2 on days 1, 15, and 29). Each cohort had 3 patients, except cohorts 4 and 6, which included 9 and 10 patients. Safety was the primary focus, with secondary efficacy targeting ≥ 1 log MRD reduction or bone marrow negativity.
The results showed 31 patients, with 22.6% (7 patients) experiencing a transient neutrophil count decrease (two grade 3, others ≤ grade 2). No infusion-related reaction or dose-limiting toxicity was observed. Most adverse events were mild to moderate, with frequent hematologic and lab abnormalities. The response rate was 35% per criteria. 2 patients sustained MRD negativity. Applying a 45 mg/m2 FLYSYN dose, either singly or cumulatively, resulted in a 46% response rate, whereas 28% responded at lower doses.
They concluded that FLYSYN monotherapy is a promising new treatment for AML patients with MRD.