Phase I safety, pharmacokinetic, and biomarker study of BIBF 1120, an oral triple tyrosine kinase inhibitor in patients with advanced solid tumors

Isamu Okamoto, Hiroyasu Kaneda, Taroh Satoh, Wataru Okamoto, Masaki Miyazaki, Ryotaro Morinaga, Shinya Ueda, Masaaki Terashima, Asuka Tsuya, Akiko Sarashina, Koichi Konishi, Tokuzo Arao, Kazuto Nishio, Rolf Kaiser, Kazuhiko Nakagawa

Research output: Contribution to journalArticle

87 Citations (Scopus)


BIBF 1120 is an oral multitargeted tyrosine kinase inhibitor that blocks the activity of vascular endothelial growth factor (VEGF) and other growth factor receptors. We have done a phase I study to evaluate the safety, pharmacokinetics, and pharmacodynamic biomarkers of BIBF 1120. Patients with advanced refractory solid tumors were treated with BIBF 1120 at oral doses of 150 to 250 mg twice daily. Drug safety and pharmacokinetics were evaluated, as were baseline and post-treatment levels of circulating CD117-positive bone marrow-derived progenitor cells and plasma soluble VEGF receptor 2 as potential biomarkers for BIBF 1120. Twenty-one patients were treated at BIBF 1120 doses of 150 (n = 3), 200 (n = 12), or 250 mg twice daily (n = 6). Dose-limiting toxicities of reversible grade 3 or 4 elevations of liver enzymes occurred in 3 of 12 patients at 200 mg twice daily and 3 of 6 patients at 250 mg twice daily. Stable disease was achieved in 16 (76.2%) patients, and median progression-free survival was 113 days (95% confidence interval, 77-119 d). Pharmacokinetic analysis indicated that the maximum plasma concentration and area under the curve for BIBF 1120 increased with the dose within the dose range tested. Levels of CD117-positive bone marrow-derived progenitors and soluble VEGF receptor 2 decreased significantly during treatment over all BIBF 1120 dose cohorts. In conclusion, the maximum tolerated dose of BIBF 1120 in the current study was determined to be 200 mg twice daily, and our biomarker analysis indicated that this angiokinase inhibitor is biologically active.

Original languageEnglish
Pages (from-to)2825-2833
Number of pages9
JournalMolecular Cancer Therapeutics
Issue number10
Publication statusPublished - Oct 1 2010
Externally publishedYes


All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this