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Ref Type Journal Article
PMID (39091594)
Authors Weber U, Davies KD, Camidge DR
Title L2086F Mutant ROS1-Rearranged NSCLC Resistant to Repotrectinib Responds to Cabozantinib: A Case Report.
Journal Vol Issue Date Pages Journal Short Title
JTO clinical and research reports 5 7 2024 Jul 100673 JTO Clin Res Rep
URL
Abstract Text 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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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ROS1 rearrange ROS1 L2086F lung adenocarcinoma predicted - sensitive Cabozantinib Case Reports/Case Series Actionable In a clinical case study, Cometriq (Cabometyx, cabozantinib) treatment resulted in a partial response in a heavily pretreated patient with metastatic lung adenocarcinoma harboring a ROS1 rearrangement with ROS1 L2086F (PMID: 39091594). 39091594