Session: 637. Myelodysplastic Syndromes — Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Clinical Trials, Adults, Workforce, Diversity, Equity, Inclusion, and Accessibility (DEI/DEIA) , Diseases, Therapies, Adverse Events, Study Population
Aims: INCB 00928-105 (NCT04582539) is a phase 1/2, open-label, multicenter dose-escalation and dose-expansion study evaluating INCB000928 as monotherapy for patients with MDS- or MM-related anemia. The primary objective is to evaluate the safety and tolerability of INCB000928 monotherapy in patients with MDS or MM who present with transfusion-dependent or symptomatic anemia. Secondary objectives are to determine efficacy and pharmacokinetics of INCB000928, and to evaluate the effect of INCB000928 treatment on iron homeostasis and erythropoiesis parameters in patients with MDS or MM.
Methods: Patients ≥18 years of age with histologically confirmed MDS (or chronic myelomonocytic leukemia or unclassifiable MDS/myeloproliferative neoplasm [MPN] overlap syndrome) or MM who present with transfusion-dependent (red blood cell transfusion ≥4 units during 28 days pretreatment, or ≥4 units during 8 weeks pretreatment with hemoglobin [Hgb] <8.5 g/dL) or symptomatic anemia (baseline Hgb <10 g/dL on 3 separate occasions ≥7 days apart) are eligible to enroll. Other key inclusion criteria include ineligibility for or lack of response to standard anemia treatments including erythropoietin-stimulating agents for patients with MDS; failure of standard MM treatments including alkylating agents, glucocorticoids, immunomodulators (lenalidomide, pomalidomide, or thalidomide), proteasome inhibitors, and daratumumab; Eastern Cooperative Oncology Group performance status ≤1 (dose escalation) or ≤2 (dose expansion); and life expectancy >6 months. Key exclusion criteria include presence of MDS with ring sideroblasts or with atypical chronic myeloid leukemia, juvenile myelomonocytic leukemia, or MDS/MPN overlap syndromes with ring sideroblasts and thrombocytosis; MDS requiring cytoreductive treatment other than hydroxyurea; MDS with bone marrow and peripheral blood myeloblast count ≥10%; platelet count <50×109/L; or is a candidate for or has had prior allogeneic stem cell transplantation. Treatment with oral INCB000928 monotherapy will start at 50 mg once daily in 28-day cycles (Figure 1). Dose escalation will follow a Bayesian optimal-interval design, independently and in parallel in each disease group (MDS vs MM), to determine the maximum tolerated doses and recommended doses for expansion (RDE) for each group, based on safety, pharmacokinetic, and pharmacodynamic data as available. Dose increases will be performed up to 2-fold until a grade 2 or greater toxicity is observed; subsequent increases will be limited to ≤50% of the prior dose. It is expected that up to 24 patients will be treated in each dose escalation, and an additional 15 patients at the RDE in each dose expansion. Patients will receive treatment for up to 6 months and may continue if deriving clinical benefit and no progression occurs. Sites are open in the United States, France, and Italy.
Disclosures: Asatiani: Incyte: Current Employment, Current equity holder in publicly-traded company. Seguy: Incyte: Current Employment, Current equity holder in publicly-traded company. Zhou: Incyte: Current Employment, Current equity holder in publicly-traded company. Michot: Innate Pharma: Research Funding; MSD: Consultancy, Honoraria; GSK: Honoraria; Celgene: Honoraria; Incyte: Research Funding; H3 biomedecine: Research Funding; GSK: Consultancy, Honoraria, Research Funding; Genentech: Research Funding; Gamamabs: Research Funding; Forma: Research Funding; Exelixis: Research Funding; Eos: Research Funding; Eisai: Research Funding; Debiopharm: Research Funding; Daiichi Sankyo,: Research Funding; Clovis: Research Funding; Chugai: Research Funding; Boeringer Ingelheim: Research Funding; Celgene: Research Funding; Blueprint: Research Funding; Beigene: Research Funding; Bayer: Research Funding; Argen-x: Research Funding; Amgen: Research Funding; Agios: Research Funding; Aduro: Research Funding; Abbvie: Research Funding; ASTEX: Research Funding, Speakers Bureau; Astra Zeneca: Honoraria, Research Funding; Roche: Honoraria; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding.
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