Pimitespib (TAS-116) 是一种一流的口服选择性热休克蛋白 90 抑制剂，在日本被批准作为胃肠道间质瘤的四线治疗。这项 1 期研究评估了 pimitespib 的心脏安全性。在这项开放标签、非随机、多中心研究中，患有难治性晚期实体瘤的日本患者（年龄≥20 岁）在第 -1 天接受安慰剂，然后在第 7 天每天接受 160 mg pimitespib心脏安全性评价期1-5。在基线以及第-2、-1、1和5天进行心电图检查；在第 1 天和第 5 天采集血样。然后患者每 3 周每天接受一次 pimitespib，持续 5 天。主要终点是 pimitespib 和安慰剂之间使用 Fridericia 校正 (QTcF) 校正心率后 QT 间期的时间匹配差异。还评估了药代动力学、安全性和初步疗效。在心脏安全性可评估人群的 22 名患者中，没有观察到临床相关的 QTc 延长； QTcF 相对于基线的时间匹配变化差异的单侧 95% 置信区间上限在第 1 天和第 5 天的所有时间点均 <20 毫秒。Pimitespib 药代动力学参数与之前的数据一致，并且时间-QTcF 相对于基线的变化的匹配差异显示，随着血浆浓度的增加，没有显着增加。安全状况是可以接受的； 40% 的患者出现 3 级或以上的药物不良反应，主要是腹泻（20%）。中位无进展生存期为 3.1 个月。在患有难治性晚期实体瘤的日本患者中，pimitespib 与临床相关的 QTc 延长无关，并且不存在心血管安全问题。Pimitespib 是一种新型抗癌药物，用于治疗胃或肠癌（胃肠道间质瘤）。这项研究表明，pimitespib 对心律没有明显影响，对心脏或血管没有负面影响，并且对无法耐受标准治疗或无法从标准治疗中获益的晚期实体瘤日本患者具有良好的抗癌作用。© 2024 ）。 《癌症》由 Wiley periodicals LLC 代表美国癌症协会出版。

Pimitespib (TAS-116), a first-in-class, oral, selective heat-shock protein 90 inhibitor, is approved as fourth-line treatment for gastrointestinal stromal tumors in Japan. This phase 1 study evaluated the cardiac safety of pimitespib.In this open-label, nonrandomized, multicenter study, Japanese patients (aged ≥20 years) with refractory, advanced solid tumors received placebo on day -1, then pimitespib 160 mg daily on days 1-5 of the cardiac safety evaluation period. Electrocardiograms were conducted at baseline, and on days -2, -1, 1, and 5; and blood samples were collected on days 1 and 5. Patients then received once-daily pimitespib for 5 days every 3 weeks. The primary end point was the time-matched difference in QT interval corrected for heart rate using the Fridericia correction (QTcF) between pimitespib and placebo. Pharmacokinetics, safety, and preliminary efficacy were also assessed.Of the 22 patients in the cardiac safety-evaluable population, no clinically relevant QTc prolongation was observed; the upper bound of the one-sided 95% confidence interval for the time-matched difference in change from baseline in QTcF was <20 msec at all time points on days 1 and 5. Pimitespib pharmacokinetic parameters were consistent with previous data, and the time-matched difference in change from baseline in QTcF showed no marked increase as plasma concentrations increased. The safety profile was acceptable; 40% of patients experienced grade 3 or greater adverse drug reactions, mostly diarrhea (20%). The median progression-free survival was 3.1 months.In Japanese patients with refractory, advanced solid tumors, pimitespib was not associated with clinically relevant QTc prolongation, and there were no cardiovascular safety concerns.Pimitespib is a new anticancer drug that is being used to treat cancer in the stomach or intestines (gastrointestinal stromal tumors). This study demonstrated that pimitespib had no marked effect on heart rhythm or negative effects on the heart or blood vessels and had promising anticancer effects in Japanese patients with advanced solid tumors who were unable to tolerate or benefit from standard treatment.© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.