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Context: Mutations in the FLT3 tyrosine kinase and in IDH1/IDH2 (collectively IDHm) co-occur in up to 30% of adults with acute myeloid leukemia (AML). SEL24/MEN1703 is an orally available, first-in-class, dual PIM/FLT3 kinase inhibitor. Preliminary results from the phase 1/2 first-in-human DIAMOND-01 trial (NCT03008187) demonstrated antitumor activity of single-agent SEL24/MEN1703 in adult patients with relapsed/refractory (R/R) IDHm AML, where 3 of 8 IDHm patients responded. Objective: To report the first safety and efficacy results from an additional expansion cohort of the DIAMOND-01 trial in 20 patients with R/R IDHm AML. Design: DIAMOND-01 is a phase 1/2, open-label, multicenter study consisting of 2 parts: dose escalation and cohort expansion, including an additional expansion cohort (IDHm) that is ongoing. Patients: Patients with R/R IDHm AML and no standard therapeutic options were eligible. Intervention(s): Patients received the recommended dose of 125 mg SEL24/MEN1703 orally, once daily for 14 days over a 21-day cycle until disease progression or unacceptable toxicity. Main Outcome Measure(s): The number and frequency of adverse events (AEs; primary) and overall response rate (ORR; secondary). Results: As of 10 January 2022, 14 patients were enrolled in the IDHm cohort. Seven patients had IDH2, 1 had IDH1/2, and 4 had IDH1 mutations. Two patients had a concomitant FLT3-ITD mutation. Safety data (N=12) showed that grade ≥3 TEAEs (≥10% of patients) were pneumonia (33%) and asthenia (17%), both unrelated to the study drug. Of the 7 patients who completed ≥1 treatment cycle and had ≥1 post-baseline assessment or clear disease progression, ORR was 28.6%; 1 patient achieved a complete response with incomplete blood count recovery at cycle 3 and underwent hematopoietic stem cell transplant, and 1 patient had a partial response at cycle 4 (confirmed at cycle 7 and still on treatment). Among the 7 remaining patients, 3 discontinued before completion of cycle 1 without progression or response, and 4 patients are ongoing and have not yet undergone post-baseline assessments. Conclusions: SEL24/MEN1703 had a manageable safety profile and single-agent activity in adult patients with R/R IDHm AML and may be a feasible therapeutic option in this difficult-to-treat population.