Rovalpituzumab Tesirine: A Novel DLL3-Targeting Antibody-Drug Conjugate

Drugs R D. 2018 Dec;18(4):255-258. doi: 10.1007/s40268-018-0247-7.

Abstract

Small cell lung cancer (SCLC) comprises about 15% of all cases of lung cancer. In recent years, owing to a change in the epidemiology of smoking habits, the incidence of the tumor has decreased; however, it remains a significant challenge to global health. While the tumor has a favorable initial response to chemoradiation, relapse is invariable, and second-line regimens may be intolerable given the severity of side effects. For patients with tumors resistant to second-line regimens, no current standard regimens exist. Rovalpituzumab tesirine is a novel antibody-drug conjugate, targeting delta-like protein 3, fundamental in the downstream cellular signaling for proliferation and apoptosis. This drug is reported to have shown promise in pre-clinical and phase I trials. It appears effective in decreasing tumor burden and is reported to be well tolerated, albeit with a significant adverse effect profile. Currently, it is being studied as part of initial and subsequent line chemotherapeutic regimens; it remains to be seen if this is a viable option in the treatment of SCLC. This may add to the agents that can be used against SCLC, and help improve outcomes.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / chemistry
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Benzodiazepinones / adverse effects
  • Benzodiazepinones / chemistry
  • Benzodiazepinones / pharmacology*
  • Cell Proliferation / drug effects
  • Clinical Trials, Phase I as Topic
  • Humans
  • Immunoconjugates / adverse effects
  • Immunoconjugates / chemistry
  • Immunoconjugates / pharmacology*
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Membrane Proteins / antagonists & inhibitors*
  • Membrane Proteins / metabolism
  • Small Cell Lung Carcinoma / drug therapy*
  • Small Cell Lung Carcinoma / metabolism
  • Small Cell Lung Carcinoma / pathology

Substances

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