Evaluating Debio 1347 in Patients with FGFR Fusion-Positive Advanced Solid Tumors from the FUZE Multicenter, Open-Label, Phase II Basket Trial

Petros Grivas, Elena Garralda, Funda Meric-Bernstam, Ingo K. Mellinghoff, Lipika Goyal, James J. Harding, E. Claire Dees, Rastislav Bahleda, Nilofer S. Azad, Asha Karippot, Razelle Kurzrock, Josep Tabernero, Juha Kononen, Matthew C.H. Ng, Rutika Mehta, Nataliya V. Uboha, Frédéric Bigot, Valentina Boni, Samantha E. Bowyer, Valeriy BrederAndrés Cervantes, Nancy Chan, James M. Cleary, Mallika Dhawan, Rikke L. Eefsen, James Ewing, Donna M. Graham, Tormod K. Guren, Jin Won Kim, Krassimir Koynov, Do Youn Oh, Rebecca Redman, Chia Jui Yen, David Spetzler, Marie Claude Roubaudi-Fraschini, Valerie Nicolas-Metral, Rafik Ait-Sarkouh, Claudio Zanna, Abdallah Ennaji, Anna Pokorska-Bocci, Keith T. Flaherty

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    2 Citations (Scopus)

    Résumé

    Purpose: This multicenter phase II basket trial investigated the efficacy, safety, and pharmacokinetics of Debio 1347, an investigational, oral, highly selective, ATP-competitive, small molecule inhibitor of FGFR1–3, in patients with solid tumors harboring a functional FGFR1–3 fusion. Patients and Methods: Eligible adults had a previously treated locally advanced (unresectable) or metastatic biliary tract (cohort 1), urothelial (cohort 2), or another histologic cancer type (cohort 3). Debio 1347 was administered at 80 mg once daily, continuously, in 28-day cycles. The primary endpoint was the objective response rate. Secondary endpoints included duration of response, progression-free survival, overall survival, pharmacokinetics, and incidence of adverse events. Results: Between March 22, 2019, and January 8, 2020, 63 patients were enrolled and treated, 30 in cohort 1, 4 in cohort 2, and 29 in cohort 3. An unplanned preliminary statistical review showed that the efficacy of Debio 1347 was lower than predicted, and the trial was terminated. In total, 3 of 58 evaluable patients had partial responses, representing an objective response rate of 5%, with a further 26 (45%) having stable disease (≥6 weeks duration). Grade ≥3 treatment-related adverse events occurred in 22 (35%) of 63 patients, with the most common being hyperphosphatemia (13%) and stomatitis (5%). Two patients (3%) discontinued treatment due to adverse events. Conclusions: Debio 1347 had manageable toxicity; however, the efficacy in patients with tumors harboring FGFR fusions did not support further clinical evaluation in this setting. Our transcriptomic-based analysis characterized in detail the incidence and nature of FGFR fusions across solid tumors.

    langue originaleAnglais
    Pages (de - à)4572-4583
    Nombre de pages12
    journalClinical Cancer Research
    Volume30
    Numéro de publication20
    Les DOIs
    étatPublié - 15 oct. 2024

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