Abstract：
Pelabresib (CPI-0610), a BET protein inhibitor, is in clinical development for hematologic malignancies, given its ability to target NF-κB gene expression. The MANIFEST phase 1 study assessed pelabresib in patients with acute leukemia, high-risk myelodysplastic (MDS) syndrome, or MDS/myeloproliferative neoplasms (MDS/MPNs) (NCT02158858). Forty-four patients received pelabresib orally once daily (QD) at various doses (24-400 mg capsule or 225-275 mg tablet) on cycles of 14 d on and 7 d off. The most frequent drug-related adverse events were nausea, decreased appetite, and fatigue. The maximum tolerated dose (MTD) was 225 mg tablet QD. One patient with chronic myelomonocytic leukemia (CMML) showed partial remission. In total, 25.8% of acute myeloid leukemia (AML) patients and 38.5% of high-risk MDS patients had stable disease. One AML patient and one CMML patient showed peripheral hematologic response. The favorable safety profile supports the ongoing pivotal study of pelabresib in patients with myelofibrosis using the recommended phase 2 dose of 125 mg tablet QD.CLINICAL TRIAL REGISTRATION: NCT02158858.
摘要：
Pelabresib(CPI-0610),一种BET蛋白抑制剂,正在临床发展血液系统恶性肿瘤，鉴于其靶向NF-κB基因表达的能力。MANIFEST1期研究评估了急性白血病患者的pelabresib，高危骨髓增生异常（MDS）综合征，或MDS/骨髓增殖性肿瘤（MDS/MPNs）（NCT02158858）。44例患者每天一次（QD）以各种剂量（24-400mg胶囊或225-275mg片剂）口服pelabresib，分为14天和7天。最常见的药物相关不良事件是恶心，食欲下降,和疲劳。最大耐受剂量(MTD)为225mg片剂QD。一名慢性粒单核细胞白血病（CMML）患者显示部分缓解。总的来说,25.8%的急性髓系白血病(AML)患者和38.5%的高危MDS患者病情稳定。一名AML患者和一名CMML患者显示外周血学反应。良好的安全性支持使用推荐的2期剂量125mg片剂QD对骨髓纤维化患者进行pelabresib的关键研究。临床试验注册：NCT02158858。
