Related Experiment Video

Updated: Aug 17, 2025

A Blood-based Test for the Detection of ROS1 and RET Fusion Transcripts from Circulating Ribonucleic Acid Using Digital Polymerase Chain Reaction
10:35

A Blood-based Test for the Detection of ROS1 and RET Fusion Transcripts from Circulating Ribonucleic Acid Using Digital Polymerase Chain Reaction

Published on: April 5, 2018

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

Alexander Drilon1, Joshua C Horan2, Anupong Tangpeerachaikul2

  • 1Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York.

Cancer Discovery
|December 13, 2022
PubMed
Abstract

Insights

NVL-520 shows promise as a novel tyrosine kinase inhibitor (TKI) for ROS1-positive cancers. It effectively targets ROS1 mutations and penetrates the brain, potentially overcoming limitations of current treatments.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • ROS1 fusion-positive cancers represent a significant therapeutic challenge.
  • Earlier-generation tyrosine kinase inhibitors (TKIs) face limitations including resistance mutations and poor brain penetration.

Purpose of the Study:

  • To evaluate the preclinical profile of NVL-520, a novel ROS1 TKI.
  • To assess NVL-520's potential to overcome resistance and improve outcomes in ROS1 fusion-positive patients.

Main Methods:

  • Preclinical evaluation of NVL-520's potency and selectivity.
  • Assessment of NVL-520's activity against diverse ROS1 resistance mutations.
  • In vivo studies to determine brain penetration capabilities.

Main Results:

  • NVL-520 demonstrates potent targeting of ROS1, including key resistance mutations.
  • High selectivity for the ROS1 G2032R mutation over TRK was observed.
  • NVL-520 exhibits significant brain penetration in preclinical models.

Conclusions:

  • NVL-520 possesses distinct preclinical features suggesting it may surpass earlier-generation TKIs.
  • This novel TKI holds potential for improved efficacy in ROS1 fusion-positive patients, including those with brain metastases.

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