NVL-520 Is a Selective, TRK-Sparing, and Brain-Penetrant Inhibitor of ROS1 Fusions and Secondary Resistance Mutations

Cancer Discov. 2023 Mar 1;13(3):598-615. doi: 10.1158/2159-8290.CD-22-0968.

Abstract

The combined preclinical features of NVL-520 that include potent targeting of ROS1 and diverse ROS1 resistance mutations, high selectivity for ROS1 G2032R over TRK, and brain penetration mark the development of a distinct ROS1 TKI with the potential to surpass the limitations of earlier-generation TKIs for ROS1 fusion-positive patients. This article is highlighted in the In This Issue feature, p. 517.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aminopyridines
  • Brain
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Humans
  • Lactams
  • Lactams, Macrocyclic / pharmacology
  • Lung Neoplasms* / genetics
  • Mutation
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins / genetics
  • Pyrazoles

Substances

  • Protein-Tyrosine Kinases
  • Aminopyridines
  • Lactams, Macrocyclic
  • Lactams
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Pyrazoles
  • ROS1 protein, human