Phase I study of ON 01910.Na, a novel modulator of the polo-like kinase 1 pathway, in adult patients with solid tumors

Antonio Jimeno, Jing Li, Wells A. Messersmith, Daniel Laheru, Michelle A. Rudek, Manoj Maniar, Manuel Hidalgo, Sharyn D. Baker, Ross C. Donehower

Research output: Contribution to journalArticlepeer-review

93 Scopus citations


Purpose: We conducted a first-in-man (to our knowledge) phase I study to determine the dose-limiting toxicities (DLTs), characterize the pharmacokinetic profile, and document any antitumor activity of ON 01910.Na, a new chemical entity that arrests cancer cells in G2/M by modulating mitotic regulatory pathways including polo-like kinase 1 (Plk1). Patients and Methods: Patients had solid tumors refractory to standard therapy. ON 01910.Na was administered as a 2-hour infusion on days 1, 4, 8, 11, 15, and 18 in 28-day cycles. The starting dose was 80 mg, and an accelerated titration schedule (single-patient cohorts) was used for escalation. Pharmacokinetics were studied on days 1 and 15 of cycle 1. Results: Twenty patients (11 women and nine men; age 46 to 73 years) were enrolled onto the study. Dose levels of 80, 160, 320, 480, 800, 1,280, 2,080, and 3,120 mg were evaluated in single-patient cohorts. A DLT and additional grade 2 toxicities made the 4,370-mg dose (n = 6) not tolerable, and the next lower dose cohort (3,120 mg) was expanded to six assessable patients. Toxicities were skeletal, abdominal, and tumor pain; nausea; urge to defecate; and fatigue. Hematologic toxicity was infrequent and mild. ON 01910.Na pharmacokinetics were characterized by a rapid distribution phase (distribution half-life, 1 hour) and a relatively slow elimination phase (elimination half-life, 27 hours). A refractory ovarian cancer patient had an objective response after four cycles and remained progression free for 24 months. Conclusion: ON 01910.Na showed a distinct but moderate toxicity pattern. The recommended phase II dose of ON 01910.Na with this schedule of administration is 3,120 mg. Single-agent activity was documented in an ovarian cancer patient.

Original languageEnglish (US)
Pages (from-to)5504-5510
Number of pages7
JournalJournal of Clinical Oncology
Issue number34
StatePublished - Dec 1 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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