医学
套细胞淋巴瘤
皮疹
不利影响
淋巴瘤
内科学
慢性淋巴细胞白血病
伊布替尼
胃肠病学
耐火材料(行星科学)
滤泡性淋巴瘤
肿瘤科
癌症研究
白血病
生物
天体生物学
作者
Loretta J. Nastoupil,Sattva S. Neelapu,R. Eric Davis,Felipe Samaniego,Nathan Fowler,Jason R. Westin,Hun Ju Lee,Michael Wang,Fredrick B. Hagemeister,Alexander Cecil,Julian A. T. Dow,Kemal Haque,Franck A. Silva,Andrew Whale,Letitia Lensun,Elisabeth A. Bone,Hilary McElwaine-Johnn,Philip Beer
标识
DOI:10.1080/10428194.2021.1957874
摘要
PI3-kinase p110δ is mainly expressed in lymphocytes and is an attractive therapeutic target in B cell lymphomas. Targeting p110β may further suppress tumor growth and overcome escape mechanisms. KA2237 is an oral, potent, dual p110β/p110δ inhibitor. In preclinical studies, KA2237 inhibited p110β- and p110δ-dependent AKT activation and suppressed proliferation of diverse hematological and epithelial tumors. Twenty-one patients received KA2237 in a first-in-human phase I study (NCT02679196; diffuse large B cell, n = 8; follicular, n = 5; mantle cell, n = 3; chronic lymphocytic leukemia/small lymphocytic lymphoma, n = 3; marginal zone, n = 1; Waldenstrom's, n = 1). Median age 69; median prior therapies 3. Eighty-six percent of patients experienced treatment-related adverse events (TRAEs). Forty-three percent of patients experienced grade ≥3 TRAEs, with rash (n = 3), pneumonia (n = 3), transaminitis (n = 2), and pneumonitis (n = 2) being most common. Thirty-three percent discontinued treatment due to adverse events. KA2237 induced objective responses in indolent and aggressive lymphoma (overall response rate 37%; complete response n = 4, partial response n = 3).
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