JTO Clinical and Research Reports (Jul 2024)

L2086F Mutant ROS1-Rearranged NSCLC Resistant to Repotrectinib Responds to Cabozantinib: A Case Report

  • Urs Weber, MD,
  • Kurtis D. Davies, PhD,
  • D. Ross Camidge, MD, PhD

Journal volume & issue
Vol. 5, no. 7
p. 100673

Abstract

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Repotrectinib, licensed in November 2023, is a novel ROS1 tyrosine kinase inhibitor (TKI) with activity against G2032R, the most common resistance mutation to prior generations of ROS1 TKIs. Here, we report a case of a patient who was heavily pretreated, with advanced L1951R and L2026M mutated ROS1-rearranged NSCLC, who initially responded to repotrectinib but later developed further on-target resistance with the emergence of an L2086F mutation. The disease then responded to cabozantinib, a separate class of ROS1 TKI with preclinical activity against L2086F.

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