L2086F mutant ROS1 rearranged NSCLC resistant to repotrectinib responds to cabozantinib: a case report

Repotrectinib, licensed in November 2023, is a novel ROS1 TKI with activity against G2032R, the most common resistance mutation to prior generations of ROS1 TKIs. Here we report a case of a heavily pre-treated patient with advanced L1951R and L2026M mutated ROS1 rearranged NSCLC who initially responded to repotrectinib, but then 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.