NOVeL treatMeNts tO OVercOMe tKI resIstaNce
2014
BACkgROunD The efficacy of current TKIs in advanced NSCLC possessing activating mutations in the EGFR is limited by the emergence of treatment resistance. Approximately 60% of cases of TKI resistance are attributable to the emergence of the T790M mutation. CO-1686 is a novel oral, covalent TKI that specifically targets both known activating mutations in EGFR as well as the T790M resistance mutation, while sparing wild-type (WT) EGFR. This phase I/II trial evaluated CO-1686 in a population of patients with EGFR-mutant NSCLC that had progressed on previous EGFR TKI treatment. All patients underwent repeat biopsy to facilitate EGFR genotyping, and endpoints included safety, pharmacokinetics and efficacy.
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