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

• Published in: JTO clinical and research reports Vol. 4; no. 11; p. 100555
• Main Authors: Pizzutilo, Elio Gregory, Agostara, Alberto Giuseppe, Roazzi, Laura, Romanò, Rebecca, Motta, Valentina, Lauricella, Calogero, Marrapese, Giovanna, Cerea, Giulio, Signorelli, Diego, Veronese, Silvio Marco, Giannetta, Laura Giuseppina, Sartore-Bianchi, Andrea, Siena, Salvatore
• Format: Report
• Language: English
• Published: 01.11.2023
• ISSN: 2666-3643
• DOI: 10.1016/j.jtocrr.2023.100555

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.