Originally published as JCO Early Release 10.1200/JCO.2008.21.1862 on August 17 2009

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Multicenter Phase II Trial of YM155, a Small-Molecule Suppressor of Survivin, in Patients With Advanced, Refractory, Non–Small-Cell Lung Cancer

From the Vrije Universiteit Medical Center, Amsterdam; Erasmus Medical Center, Rotterdam; Astellas Pharma Europe BV, Leiderdorp, the Netherlands; Charles University, 3rd Faculty of Medicine and Teaching Hospital Bulovka; Charles University, 2nd Faculty of Medicine and Teaching Hospital Motol, Prague; Teaching Hospital Ostrava-Poruba, Ostrava-Poruba; Nemocnice Chomutov, Chomutov; and the Onkologicke Centrum JG Mendla, Novy Jicin, Czech Republic.

Corresponding author: Giuseppe Giaccone, MD, PhD, Medical Oncology Branch, National Cancer Institute, 10 Center Dr, Bethesda, MD 20892; e-mail: giacconeg{at}mail.nih.gov.

Purpose To evaluate the antitumor activity and safety of YM155, a novel, small-molecule suppressor of survivin, as single-agent therapy in patients with previously treated, advanced non–small-cell lung cancer (NSCLC).

Patients and Methods Patients with stage IIIb/IV NSCLC who had experienced treatment failure during one or two prior chemotherapy regimens (at least one of which was platinum based) received YM155 as a continuous intravenous infusion (4.8 mg/m²/d) over 168 hours followed by observation for 14 days in 21-day treatment cycles. The primary end point was objective tumor response rate (ORR). Secondary end points included duration of stable disease (SD), progression-free survival (PFS), overall survival (OS), safety and pharmacokinetic profiles, and pharmacodynamic evaluations.

Results Thirty-seven patients received YM155. Two patients achieved a confirmed partial response, with an ORR of 5.4% (95% CI, 0.7% to 18.2%). An additional 14 patients (37.8%) achieved SD resulting in a disease control rate of 43.2% (95% CI, 27.1% to 60.5%). Median duration of PFS was 1.7 months (95% CI, 1.3 to 2.8 months). Median duration of OS was 6.6 months (95% CI, 4 to 12.2 months), with a 1-year survival rate of 35.1%. Treatment with YM155 was well tolerated with the majority of treatment discontinuations not treatment related.

Conclusion YM155 exhibited modest single-agent activity in patients with refractory, advanced NSCLC. A favorable safety/tolerability profile was reported. Further evaluation of YM155 in combination with chemotherapy and other targeted agents may be warranted.

Supported by Astellas Pharma Europe BV.

Presented in part at the 5th International Symposium on Targeted Anticancer Therapies coorganized with the European Society for Medical Oncology, Amsterdam, the Netherlands, March 8- 10, 2007; and the 2007 American Association for Cancer Research-National Cancer Institute–European Organisation for the Research and Treatment of Cancer International Conference on Molecular Targets and Cancer Therapeutics, San Francisco, CA, October 22-26, 2007.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on JCO.org.

Clinical trial information can be found for the following: NCT00328588 [ClinicalTrials.gov] .

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