Trial Update from IMproveMF, an Ongoing, Open-Label, Dose-Escalation and -Expansion, Phase 1/1B Trial to Evaluate the Safety, Pharmacokinetics, and Clinical Activity of the Novel Combination of Imetelstat with Ruxolitinib in Patients with Intermediate-1, Intermediate-2, or High-Risk Myelofibrosis (MF)

作者：John Mascarenhas, Salman Otoukesh, Terrence Bradley, Bart L. Scott, Habte Yimer, Souria Dougherty, Lixian Peng, Fei Huang, Ying Wan, Faye Feller, Vivian Rodolf, Judy Ho, Tymara Berry, Andrew Kuykendall · 发表于：Blood · 年份：2024 · DOI：10.1182/blood-2024-203800 · 被引用次数：5 · 研究领域：Myeloproliferative Neoplasms: Diagnosis and Treatment、Chronic Myeloid Leukemia Treatments

Introduction: MF is a progressive myeloproliferative neoplasm commonly associated with driver mutations in JAK2, CALR, or MPL genes. Janus kinase inhibitors (JAKi; eg, ruxolitinib [RUX]) can reduce MF spleen size and symptom burden but do not have disease-modifying activity. Imetelstat (IME), a first-in-class direct and competitive inhibitor of telomerase enzymatic activity approved in the United States (US) to treat patients (pts) with transfusion-dependent low- to intermediate (INT)-1-risk myelodysplastic syndromes, demonstrated potential survival improvements and disease-modifying activity in the phase 2 IMbark trial (NCT02426086) in pts with MF relapsed or refractory to JAKis. Preclinical evidence demonstrated that the combination of IME+RUX reduced disease burden better than either agent alone. IMproveMF (NCT05371964) aims to evaluate safety, pharmacokinetics (PK), and clinical activity of IME+RUX in pts with INT-1/INT-2/high-risk (HR) MF. Methods: IMproveMF is an ongoing, open-label, single-arm, multicenter, phase 1/1b trial (part 1: dose escalation; part 2: dose confirmation and expansion) of IME+RUX in adults with Dynamic International Prognostic Scoring System INT-1, INT-2, or HR MF with an Eastern Cooperative Oncology Group performance status of ≤2 and peripheral blood and bone marrow blasts <10%. In part 1 (up to 21 pts), RUX treatment is required for ≥12 weeks with a stable dose for ≥4 weeks immediately before adding IME; IME is administered intravenously a...