Mary Crowley Medical Research Center, Dallas, Texas, USA
Vall d'Hebron University Hospital and Universitat Autonoma de Barcelona, Barcelona, Spain.
Oncologist. 2018 Apr;23(4):401-e38. doi: 10.1634/theoncologist.2017-0691. Epub 2018 Mar 28.
A phase I study of the pan-class I phosphoinositide 3-kinase inhibitor pilaralisib (in capsule formulation) in advanced solid tumors established the maximum tolerated dose as 600 mg once daily.The current study investigated pilaralisib in tablet formulation.Pilaralisib tablets were associated with a favorable safety profile and preliminary antitumor activity.Based on pharmacokinetic data, the recommended phase II dose of pilaralisib tablets was established as 400 mg once daily.
A phase I trial of pilaralisib, an oral pan-class I phosphoinositide 3-kinase (PI3K) inhibitor, established the maximum tolerated dose (MTD) of the capsule formulation in patients with advanced solid tumors as 600 mg once daily. This phase I study investigated pilaralisib in tablet formulation.
Patients with advanced solid tumors received pilaralisib tablets (100-600 mg once daily). Primary endpoints were MTD and safety; secondary and exploratory endpoints included pharmacokinetics (PK), pharmacodynamics, and efficacy.
Twenty-two patients were enrolled. No dose-limiting toxicities (DLTs) were reported. The most common treatment-related adverse events were diarrhea (40.9%), fatigue (40.9%), decreased appetite (22.7%), and hyperglycemia (22.7%). Pilaralisib plasma exposure did not appear to increase dose-proportionally. Steady-state exposure was higher with pilaralisib tablet formulation at 400 mg than with pilaralisib capsule formulation at 400 or 600 mg (mean area under the curve [AUC] 2,820,000 ng × h/mL vs. 2,653,000 and 1,930,000 ng × h/mL, respectively). Of 18 evaluable patients, 2 (11.1%) had a partial response (PR).
Pilaralisib tablets were associated with a favorable safety profile and preliminary antitumor activity. MTD was not determined. The recommended phase II dose for pilaralisib tablets, based on PK data, was 400 mg once daily.
一项 I 期研究表明，泛 I 类磷酸肌醇 3-激酶（PI3K）抑制剂 pilaralisib（胶囊制剂）在晚期实体瘤中的最大耐受剂量为每日一次 600mg。本研究调查了片剂制剂的 pilaralisib。pilaralisib 片剂与良好的安全性特征和初步抗肿瘤活性相关。基于药代动力学数据，确定了 pilaralisib 片剂的推荐 II 期剂量为每日一次 400mg。
一项 I 期试验表明，口服泛 I 类磷酸肌醇 3-激酶（PI3K）抑制剂 pilaralisib 在晚期实体瘤中的最大耐受剂量（MTD）为胶囊制剂每日一次 600mg。这项 I 期研究调查了片剂制剂的 pilaralisib。
晚期实体瘤患者接受 pilaralisib 片剂（每日一次 100-600mg）。主要终点是 MTD 和安全性；次要和探索性终点包括药代动力学（PK）、药效学和疗效。
22 名患者入组。未报告剂量限制毒性（DLTs）。最常见的治疗相关不良事件是腹泻（40.9%）、疲劳（40.9%）、食欲下降（22.7%）和高血糖（22.7%）。pilaralisib 血浆暴露似乎没有呈剂量比例增加。pilaralisib 片剂制剂 400mg 时的稳态暴露高于 pilaralisib 胶囊制剂 400mg 和 600mg（平均 AUC2，820，000ng×h/mL 与 2653，000 和 1930，000ng×h/mL 相比）。18 名可评估患者中，2 名（11.1%）有部分缓解（PR）。
pilaralisib 片剂与良好的安全性特征和初步抗肿瘤活性相关。未确定 MTD。基于 PK 数据，pilaralisib 片剂的推荐 II 期剂量为每日一次 400mg。
