An open-label, phase 1 study evaluating safety, tolerability, and pharmacokinetics of linifanib (ABT-869) in Japanese patients with solid tumors

Hajime Asahina, Yosuke Tamura, Hiroshi Nokihara, Noboru Yamamoto, Yoshitaka Seki, Takashi Shibata, Yasushi Goto, Maki Tanioka, Yasuhide Yamada, Andrew Coates, Yi Lin Chiu, Xiaohui Li, Rajendra Pradhan, Peter J. Ansell, Evelyn M. McKeegan, Mark D. McKee, Dawn M. Carlson, Tomohide Tamura

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


Purpose: This phase 1 study assessed the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of linifanib in Japanese patients with advanced solid tumors. Methods: Patients were assigned to one of four sequential cohorts (0.05, 0.10, 0.20, or 0.25 mg/kg) of oral, once-daily linifanib on a 21-day cycle. Adverse events (AEs) were assessed per common terminology criteria for adverse events v3.0; tumor responses were assessed by response evaluation criteria in solid tumors. Results: Eighteen patients were enrolled. Eleven (61%) received ≥3 prior therapies. Dose-limiting toxicities were Grade 3 ALT increase (0.10 mg/kg linifanib) and Grade 1 T-wave inversion (0.25 mg/kg linifanib) requiring dose interruption for >7 days and discontinuation on day 29. The most common linifanib-related AE was hypertension. Other significant treatment-related AEs included proteinuria, fatigue, and palmar-plantar erythrodysaesthesia. Linifanib pharmacokinetics were dose-proportional across 0.10-0.25 mg/kg. Two patients (11.1%) had confirmed partial responses, 12 had a best response of stable disease (11 had stable disease for ≥12 weeks), and four patients were not evaluable due to incomplete data. Four patients (lung cancer, breast cancer, thymic cancer, sarcoma) have continued linifanib for ≥48 weeks (range, 48-96+ weeks). Conclusion: Linifanib was well tolerated with promising preliminary clinical activity in Japanese patients. Laterphase global studies examining linifanib efficacy will include Japanese patients.

Original languageEnglish
Pages (from-to)1477-1486
Number of pages10
JournalCancer Chemotherapy and Pharmacology
Issue number6
Publication statusPublished - Jun 2012
Externally publishedYes


  • Angiogenesis
  • Japanese
  • Linifanib (ABT-869)
  • Solid tumors

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)


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