Phase I dose-escalation study of buparlisib (BKM120), an oral pan-class I PI3K inhibitor, in Japanese patients with advanced solid tumors

Cancer Sci. 2014 Mar;105(3):347-53. doi: 10.1111/cas.12350. Epub 2014 Feb 13.


Buparlisib (BKM120) is an oral pan-phosphatidylinositol 3-kinase inhibitor, targeting all four isoforms of class I PI3K (α, β, γ and δ). This open-label Phase I dose-escalation study was conducted to determine the maximum tolerated dose of continuous daily buparlisib in Japanese patients with advanced solid tumors. Secondary objectives included safety and tolerability, pharmacokinetics, antitumor activity and pharmacodynamic marker changes. Fifteen patients were treated at 25 mg/day (n = 3), 50 mg/day (n = 3) and 100 mg/day (n = 9) dose levels. One dose-limiting toxicity of Grade 4 abnormal liver function occurred at 100 mg/day. Considering the safety profile and the maximum tolerated dose in the first-in-man study of buparlisib in non-Japanese patients, further dose escalation was stopped and 100 mg/day was declared the recommended dose. The most common treatment-related adverse events were rash, abnormal hepatic function (including increased transaminase levels), increased blood insulin levels and increased eosinophil count. Hyperglycemia was experienced by two patients, one Grade 1 and one Grade 4, and mood alterations were experienced by three patients, two Grade 1 and one Grade 2. Pharmacokinetic results showed that buparlisib was rapidly absorbed in a dose-proportional manner. Best overall response was stable disease for six patients, including one unconfirmed partial response. In these Japanese patients with advanced solid tumors, buparlisib had a manageable safety profile, with similar pharmacokinetics to non-Japanese patients. The recommended dose of 100 mg/day will be used in future studies of buparlisib in Japanese patients.

Keywords: BKM120; Japanese patients; buparlisib.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aminopyridines / administration & dosage*
  • Aminopyridines / adverse effects
  • Aminopyridines / pharmacokinetics
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Area Under Curve
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Drug Administration Schedule
  • Female
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Japan
  • Lymphatic Metastasis
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Morpholines / administration & dosage*
  • Morpholines / adverse effects
  • Morpholines / pharmacokinetics
  • Phosphoinositide-3 Kinase Inhibitors*
  • Treatment Outcome
  • Young Adult


  • Aminopyridines
  • Antineoplastic Agents
  • Morpholines
  • NVP-BKM120
  • Phosphoinositide-3 Kinase Inhibitors