Prevalence of Delta-like protein 3 expression in patients with small cell lung cancer

Lung Cancer. 2018 Jan;115:116-120. doi: 10.1016/j.lungcan.2017.11.018. Epub 2017 Nov 22.

Abstract

Objectives: Rovalpituzumab tesirine (Rova-T), an antibody-drug conjugate directed against Delta-like protein 3 (DLL3), is under development for patients with small cell lung cancer (SCLC) positive for this protein. However, the prevalence of DLL3 expression and its association with patient ethnicity and other characteristics have remained unclear.

Materiais and methods: Tumor samples from 63 patients with SCLC were subjected to immunohistochemical staining for DLL3. The relation of patient characteristics including sex, age, disease stage, and smoking history to DLL3 expression status was analyzed.

Results and conlusions: Fifty-two patients (83%) were positive for DLL3 expression, with 20 patients (32%) being positive in at least 50% of cancer cells (DLL3-high). DLL3 expression was not associated with any of the patient characteristics examined. In addition, overall survival did not differ between DLL3-high and DLL3-low patients. Our results reveal that DLL3 is expressed in tumor specimens from most patients with SCLC, and they should inform the undertaking of clinical trials of Rova-T including an ongoing phase I study (NCT03086239) in Japan as well as global phase III trials (NCT03061812 and NCT03033511).

Keywords: Delta-like protein 3; Rovalpituzumab tesirine; Small cell lung cancer.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Benzodiazepinones / therapeutic use*
  • Clinical Trials as Topic
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunoconjugates / therapeutic use*
  • Immunotherapy / methods*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / immunology
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Japan
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Small Cell Lung Carcinoma / drug therapy
  • Small Cell Lung Carcinoma / genetics*
  • Small Cell Lung Carcinoma / mortality
  • Survival Analysis

Substances

  • Antibodies, Monoclonal, Humanized
  • Benzodiazepinones
  • DLL3 protein, human
  • Immunoconjugates
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • rovalpituzumab tesirine

Associated data

  • ClinicalTrials.gov/NCT03086239
  • ClinicalTrials.gov/NCT03061812
  • ClinicalTrials.gov/NCT03033511