Clinical Lymphoma, Myeloma & Leukemia, Vol.22, Suppl.2 - October 2022

Abstracts Clinical Lymphoma, Myeloma & Leukemia October 2022 S244 Menarini Group, Florence, Italy. 17 Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, USA Co n text: Mutations in the FLT3 tyrosine kinase and in IDH1/ IDH2 (collectively IDH m) co-occur in up to 30% of adults with acute myeloid leukemia (AML). SEL24/MEN1 7 03 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 (NCT0300818 7 ) demonstrated antitumor activity of single-agent SEL24/MEN1 7 03 in adult patients with relapsed/refractory (R/R) IDH m AML, where 3 of 8 IDH m patients responded. Objecti v e: To report the first safety and efficacy results from an additional expansion cohort of the DIAMOND-01 trial in 20 patients with R/R IDH m AML. D esig n : 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 ( IDH m) that is ongoing. Patie n ts: Patients with R/R IDH m AML and no standard therapeutic options were eligible. I n ter v e n tio n (s): Patients received the recommended dose of 125 mg SEL24/MEN1 7 03 orally, once daily for 14 days over a 21-day cycle until disease progression or unacceptable toxicity. Mai n Outco m e 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 IDH m 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 (1 7 %), 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. Co n clusio n s: SEL24/MEN1 7 03 had a manageable safety profile and single-agent activity in adult patients with R/R IDH m AML and may be a feasible therapeutic option in this difficult-to-treat population. Keywords: AML, acute myeloid leukemia, FLT3-ITD , FLT3 inhibitor, IDH mutation, PIM kinase, Trial-in-Progress AML-391 Phase 1/2, Open-Label, Dose Escalation, Dose Expansion Study of Menin Inhibitor DSP-5336 in Adult Patients With Acute Leukemia With and Without Mixed-Lineage Leukemia (MLL)–Rearrangement or Nucleophosmin 1 (NPM1) Mutation Naval Daver MD 1 , John Affinito MD 2 , Hongliang Cai PhD 2 , Hanna Dobrowolska PhD 2 , Ken Eguchi PhD 3 , Jay Stoudemire PhD 2 , Akinobu Watanabe PhD 2 , Matthew Hitron MD 2 1 Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, USA. 2 Sumitomo Pharma Oncology, Inc., Cambridge, USA. 3 Sumitomo Pharma Co., Ltd., Osaka, Japan Patients who relapse after initial acute leukemia (AL) treatment have median survival <6months for AML and <1 y for ALL, especially AML or ALL with MLL rearrangements (MLLr) or relapsed AML with NPM1 mutations. Translocations of the MLL gene (5% to 10% of adult patients) produce an aggressive subtype, with a median overall survival (OS) of approximately 9 months. The NPM1 mutation (NPM1m) occurs in 30%–35% of adult de novo AML and is associated with a favorable prognosis. However, 40%–50% of these patients have concurrent FLT3 -internal tandem duplication mutations negating this favorability. DSP-5336, a novel oral small- molecule, was developed to prevent menin protein binding to MLL fusion proteins that drive leukemogenesis. Nonclinical DSP-5336 studies showed selective growth inhibition against human AL cell lines with MLLr or NPM1m. Evidence of antitumor activity and survival advantage was demonstrated in 3 AML xenograft models with MLLr and/or NPM1m. Treatment with DSP-5336 may reduce leukemic cells and benefit patients with relapsed or refractory (R/R) MLLr or NPM1m AML or patients with R/R MLLr ALL. An open- label, single-arm, phase 1/2 study (NCT04988555) will evaluate the safety and efficacy of DSP-5336 and determine the recommended phase 2 dose (RP2D) in adults aged  18 y with relapsed/refractory AML or ALL after at least one line of therapy. Key inclusion criteria are ECOG performance status 0–2 and adequate organ function. Patients will be dosed twice daily in 28-day cycles. In phase 1, 21–30 patients will be enrolled into multiple dose cohorts (1–6 patients per dose level), with dose escalation determined using a two-parameter Bayesian logistic regression model. The RP2D will be informed by the maximum biologic effect or maximum tolerated dose, whichever is lower. The phase 2 study will include two arms (R/R AML with MLLr and R/R AML with NPM1m). Patients will be treated at the RP2D to evaluate clinical activity and safety and monitored using Bayesian posterior probability to optimize enrollment with Bayesian stopping rules. Bayesian monitoring of responses begins after the first 10 enrolled patients are evaluable for efficacy. This study is recruiting in the United States and Japan. Keywords: AML, acute leukemia, MLL rearrangements, NPM1m mutations, Trial-in-Progress AML-392 Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm in Pediatric Patients With Tagraxofusp, a CD123- Targeted Therapy Naveen Pemmaraju MD 1 , Branko Cuglievan MD 1 , Joseph Lasky MD 2 , Albert Kheradpour MD 3 , Nobuko Hijiya MD 4 , Anthony S. Stein MD 5 , Soheil Meshinchi MD 6 , Craig Mullen MD 7 , Emanuele Angelucci MD 8 , Luciana Vinti MD 9 , Tariq I. Mughal MD 10,11 , Anna Pawlowska MD 12 1 Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, USA. 2 Cure 4 The Kids Foundation, Las Vegas, USA. 3 Department of Pediatric Hematology and Oncology,