An open-label, phase II study of the polo-like kinase-1 (Plk-1) inhibitor, BI 2536, in patients with relapsed small cell lung cancer (SCLC)

Lung Cancer. 2017 Feb:104:126-130. doi: 10.1016/j.lungcan.2016.12.019. Epub 2016 Dec 30.

Abstract

Objectives: This phase II, open-label study was designed to evaluate the response rate to the polo-like kinase 1 (Plk-1) inhibitor BI 2536 in patients with sensitive-relapsed small cell lung cancer (SCLC). Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response, and safety.

Materials and methods: Patients were treated with the recommended phase II dose of 200mg of BI 2536 intravenously every 21days. This was a two-stage design with an early stopping rule in place if responses were not seen in at least 2 of the first 18 enrolled patients.

Results and conclusion: Twenty-three patients were enrolled in the study and 21 patients were evaluable for response. No responses were observed and all 23 patients have progressed. The median PFS was 1.4 months. Treatment was generally well tolerated and the most frequent adverse events were neutropenia, fatigue, nausea, vomiting, and constipation. BI 2536 is not effective in the treatment of sensitive relapsed SCLC. The criteria for expanding the trial to the second stage were not achieved, and the study was terminated for a lack of efficacy.

Keywords: BI 2536; Plk-1 inhibition; Polo-like kinase; Small cell lung cancer.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Administration, Intravenous
  • Adult
  • Aged
  • Cell Cycle Proteins / adverse effects
  • Cell Cycle Proteins / antagonists & inhibitors*
  • Cell Cycle Proteins / therapeutic use
  • Disease-Free Survival
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Polo-Like Kinase 1
  • Protein Serine-Threonine Kinases / adverse effects
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / therapeutic use
  • Proto-Oncogene Proteins / adverse effects
  • Proto-Oncogene Proteins / antagonists & inhibitors*
  • Proto-Oncogene Proteins / therapeutic use
  • Pteridines / administration & dosage*
  • Pteridines / adverse effects
  • Pteridines / pharmacology
  • Recurrence
  • Small Cell Lung Carcinoma / drug therapy*
  • Small Cell Lung Carcinoma / pathology
  • Smoking / epidemiology
  • Treatment Failure
  • Treatment Outcome

Substances

  • BI 2536
  • Cell Cycle Proteins
  • Proto-Oncogene Proteins
  • Pteridines
  • Protein Serine-Threonine Kinases