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.
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Weber et al. (2024) studied this question.
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