Department of GI Oncology/Gastroenterology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Department of Oncology, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan.
Target Oncol. 2019 Feb;14(1):57-65. doi: 10.1007/s11523-019-00620-0.
Focal adhesion kinase (FAK) inhibitors have demonstrated anti-tumor activity preclinically and are currently being evaluated in humans. A first-in-human study evaluating the novel FAK inhibitor BI 853520 in a predominantly Caucasian population with advanced or metastatic non-hematologic malignancies demonstrated acceptable tolerability and favorable pharmacokinetics.
This study was undertaken to investigate the safety, tolerability, and maximum tolerated dose (MTD) of BI 853520 in Japanese and Taiwanese patients with advanced solid tumors.
In this open-label, phase I, dose-finding study, BI 853520 was administered once daily (QD) in a continuous daily dosing regimen with 28-day cycles and escalating doses to sequential cohorts of patients. Twenty-one patients (62% male; median age 65 years) were treated at two sites in Japan and Taiwan.
The median duration of treatment was 1.2 months (range 0.2-7.7). As no dose-limiting toxicities were observed during cycle 1 in the 50, 100, or 200 mg cohorts, the MTD of BI 853520 was determined to be 200 mg QD. Drug-related adverse events were reported in 19 patients (90%), and all except one were of grade 1 or 2. Pharmacokinetic parameters were supportive of a once-daily dosing schedule. A confirmed objective response rate of 5% and disease control rate of 29% were achieved; median duration of disease control was 3.7 months.
This trial demonstrated a manageable and acceptable safety profile, favorable pharmacokinetics, and potential anti-tumor activity of BI 853520 in pretreated Japanese and Taiwanese patients with advanced or metastatic solid tumors.
NCT01905111.
黏着斑激酶（FAK）抑制剂在临床前表现出抗肿瘤活性，目前正在人类中进行评估。一项在主要为高加索人群中进行的、评估新型 FAK 抑制剂 BI 853520 在晚期或转移性非血液恶性肿瘤中的作用的首次人体研究显示出可接受的耐受性和良好的药代动力学特性。
本研究旨在评估 BI 853520 在日本和中国台湾地区晚期实体瘤患者中的安全性、耐受性和最大耐受剂量（MTD）。
在这项开放标签、I 期、剂量递增研究中，BI 853520 采用每日一次（QD）连续每日给药方案，每 28 天为一个周期，并按顺序递增剂量入组患者。在日本和中国台湾的两个研究中心共入组 21 例患者（62%为男性；中位年龄 65 岁）。
中位治疗持续时间为 1.2 个月（范围 0.2-7.7）。在 50、100 和 200 mg 剂量队列的第 1 周期未观察到剂量限制性毒性，因此确定 BI 853520 的 MTD 为 200 mg QD。19 例患者（90%）报告了药物相关不良事件，除 1 例外均为 1 级或 2 级。药代动力学参数支持每日 1 次给药方案。确认的客观缓解率为 5%，疾病控制率为 29%；疾病控制的中位持续时间为 3.7 个月。
这项试验表明 BI 853520 在既往治疗的日本和中国台湾地区晚期或转移性实体瘤患者中具有可管理和可接受的安全性、良好的药代动力学特征和潜在的抗肿瘤活性。
NCT01905111。
