Phase I Trial of a Tablet Formulation of Pilaralisib, a Pan-Class I PI3K Inhibitor, in Patients with Advanced Solid Tumors

Oncologist. 2018 Apr;23(4):401-e38. doi: 10.1634/theoncologist.2017-0691. Epub 2018 Mar 28.


Lessons learned: 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.

Background: 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.

Materials and methods: 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.

Results: 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 [AUC0-24] 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).

Conclusion: 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.


• 一项在晚期实体瘤中对泛I类磷脂酰肌醇‐3激酶抑制剂Pilaralisib(胶囊剂型)进行的I期研究确定了最大耐受剂量为600 mg每日一次。

• 当前研究对Pilaralisib片剂剂型进行了研究。

• 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, 将Pilaralisib片剂的推荐II期剂量确定为400 mg每日一次。


背景.Pilaralisib[一种口服泛I类磷脂酰肌醇‐3激酶(PI3K)抑制剂]的一项I期研究确定胶囊剂型在晚期实体瘤患者中的最大耐受剂量(MTD)为600 mg每日一次。本项I期研究对Pilaralisib片剂剂型进行了研究。

材料和方法.晚期实体瘤患者接受Pilaralisib片剂给药(100–600 mg每日一次)。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。

结果.22例患者入组。未报告剂量限制性毒性(DLT)。最常见的治疗相关不良事件为腹泻(40.9%)、疲乏(40.9%)、食欲下降(22.7%)和高血糖症(22.7%)。Pilaralisib血浆暴露量未呈现与剂量成比例增加。400mg Pilaralisib片剂剂型的稳态暴露量高于400或600mg Pilaralisib胶囊剂型的稳态暴露量[平均曲线下面积(AUC0–24)分别为2 820 000 ng x h/mL、2 653 000和1 930 000 ng x h/mL]。在18例可评价患者中, 2例(11.1%)达到部分缓解(PR)。

结论.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400 mg每日一次。

Trial registration: NCT00486135.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Phosphoinositide-3 Kinase Inhibitors*
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinoxalines / administration & dosage
  • Quinoxalines / adverse effects
  • Quinoxalines / pharmacokinetics
  • Quinoxalines / therapeutic use*
  • Safety
  • Sulfonamides / administration & dosage
  • Sulfonamides / adverse effects
  • Sulfonamides / pharmacokinetics
  • Sulfonamides / therapeutic use*
  • Tablets
  • Treatment Outcome


  • Antineoplastic Agents
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • Quinoxalines
  • Sulfonamides
  • Tablets
  • XL147

Associated data