JTO Clinical and Research Reports (Nov 2023)

Repotrectinib Overcomes F2004V Resistance Mutation in ROS1-Rearranged NSCLC: A Case Report

  • Elio Gregory Pizzutilo, MD,
  • Alberto Giuseppe Agostara, MD,
  • Laura Roazzi, MD,
  • Rebecca Romanò, MD,
  • Valentina Motta, PhD,
  • Calogero Lauricella, PhD,
  • Giovanna Marrapese, PhD,
  • Giulio Cerea, MD,
  • Diego Signorelli, MD, PhD,
  • Silvio Marco Veronese, PhD,
  • Laura Giuseppina Giannetta, MD,
  • Andrea Sartore-Bianchi, MD,
  • Salvatore Siena, MD

Journal volume & issue
Vol. 4, no. 11
p. 100555

Abstract

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ROS1 tyrosine kinase inhibitors (TKIs) were found to provide a substantial clinical benefit for patients with advanced ROS1-positive (ROS1+) NSCLC. Nevertheless, TKI resistance inevitably develops with different mechanisms, preventing prolonged responses. For this reason, next-generation compounds are under clinical development. ROS1 F2004 substitutions have been previously detected on circulating tumor DNA of patients progressing to entrectinib. Hereby, we report the case of a patient with ROS1+ NSCLC in which F2004V-acquired mutation was detected on a site of disease progression, after entrectinib and crizotinib failure. A subsequent treatment with next-generation TKI repotrectinib led to disease response, providing the first clinical evidence of activity of repotrectinib against F2004V resistance mutation.

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