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

Urs Weber; Kurtis D Davies; D Ross Camidge

doi:10.1016/j.jtocrr.2024.100673

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

JTO Clin Res Rep. 2024 Apr 1;5(7):100673. doi: 10.1016/j.jtocrr.2024.100673. eCollection 2024 Jul.

Authors

Urs Weber¹, Kurtis D Davies², D Ross Camidge¹

Affiliations

¹ Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
² Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.

Abstract

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.

Keywords: Cabozantinib; Case report; L2086F; ROS1; Repotrectinib.

Publication types

Case Reports