中性粒细胞减少症
伊马替尼
医学
贫血
临床终点
胃肠病学
恶心
临床研究阶段
甲磺酸伊马替尼
内科学
肿瘤科
外科
毒性
临床试验
髓系白血病
作者
Jin‐Hee Ahn,Jeeyun Lee,Changhee Park,Seung‐Hoon Beom,Seung Hyun Kim,Young Han Lee,Kum-Hee Yun,Jeong Eun Kim,Wooyeol Baek,Yoon Dae Han,Sangkyum Kim,Hyang Joo Ryu,Inkyung Jung,Joo-Hee Lee,Hong In Yoon,Hyo Song Kim
标识
DOI:10.1158/1078-0432.ccr-23-2823
摘要
The study was to determine the activity and safety of the TGF-β inhibitor vactosertib in combination with imatinib in patients with desmoid tumors.In this investigator-initiated, open-label, multicenter, phase Ib/II trial, patients with desmoid tumors not amenable to locoregional therapies (surgery and/or radiotherapy) or with disease progression following at least one treatment were enrolled. Participants were administered 400 mg imatinib daily in combination with vactosertib (5 days on and 2 days off, twice a day) every 28 days. In phase Ib, the vactosertib dose was set at 100 mg (level -1) and 200 mg (level 1) to determine the recommended phase II dose (RP2D). Phase II assessed the efficacy, with the primary endpoint being progression-free rate (PFR) at 16 weeks.No dose-limiting toxicities were observed during phase Ib; therefore RP2D was defined at doses of 400 mg imatinib daily in combination with 200 mg vactosertib. Of the 27 patients evaluated, 7 (25.9%) achieved a confirmed partial response and 19 (70.4%) were stable. The PFR at 16 weeks and 1 year were 96.3% and 81.0%, respectively. Most toxicities were mild to moderate myalgia (n = 10, 37%), anemia (n = 10, 37%), and nausea (n = 9, 33.3%). Common grade 3 to 4 toxicities included neutropenia (n = 6, 22.2%) and anemia (n = 5, 18.5%).The vactosertib and imatinib combination was well tolerated, with promising clinical activity in patients with progressive, locally advanced desmoid tumors. This is the first study investigating a novel target agent, a TGF-β inhibitor, in this rare and difficult-to-treat desmoid tumor.
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