Safety and Efficacy of Bromodomain and Extra-Terminal Inhibitor INCB057643 in Patients with Relapsed or Refractory Myelofibrosis and Other Advanced Myeloid Neoplasms: A Phase 1 Study

作者：J. Watts, Anthony M. Hunter, Alessandro Vannuchhi, V. Gupta, S. Tantravahi, A. Iurlo, Brandon McMahon, F. Palandri, M. G. Gómez Casares, J. Yuda, E. Searle, A. Halpern, Rosa Ayala, Akihiro Tomita, Blanca Xicoy, P. Bose, Brandi N Reeves, Xuejun Chen, Lea M Burke, F. Zhou, Fred Zheng, P. Vachhani · 发表于：Blood · 年份：2024 · DOI：10.1182/blood-2024-200925 · 被引用次数：5

Introduction: Bromodomain and extra-terminal (BET) proteins are epigenetic readers that regulate expression of critical oncoproteins involved in the pathophysiology of hematologic malignancies, including myelofibrosis (MF). In a previous phase 1/2 clinical trial, INCB057643 (an oral, small-molecule BET inhibitor) evaluated as monotherapy or combination (combo) with the Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib (RUX) showed favorable tolerability and encouraging clinical activity in patients (pts) with advanced MF. Methods: This ongoing phase 1, open-label 3+3 dose-escalation/expansion study (NCT04279847) is evaluating INCB057643 as monotherapy (part 1; 4 mg→12 mg once daily [qd]) in adults with relapsed/refractory MF, essential thrombocythemia (ET), myelodysplastic syndromes (MDS), or MDS/myeloproliferative neoplasm (MPN) overlap syndromes, or as combo therapy (part 2; 4 mg qd→part 1 maximum tolerated dose) with RUX in adults with MF who have suboptimal response to RUX. Primary endpoints are safety/tolerability, including dose-limiting toxicities (DLTs). Secondary endpoints include spleen volume (SV) response (≥35% reduction from baseline [BL] in SV [SVR35] at Week 24), symptom response (≥50% reduction from BL in MPN-Symptom Assessment Form total symptom score [TSS50] at Week 24), and anemia response (hemoglobin increase ≥1.5 g/dL from BL [if transfusion independent at BL] or achieving transfusion independence [if dependent at BL] for ≥12 weeks). Results: Among pts tre...