TY - JOUR
T1 - Evaluating Debio 1347 in Patients with FGFR Fusion-Positive Advanced Solid Tumors from the FUZE Multicenter, Open-Label, Phase II Basket Trial
AU - Grivas, Petros
AU - Garralda, Elena
AU - Meric-Bernstam, Funda
AU - Mellinghoff, Ingo K.
AU - Goyal, Lipika
AU - Harding, James J.
AU - Dees, E. Claire
AU - Bahleda, Rastislav
AU - Azad, Nilofer S.
AU - Karippot, Asha
AU - Kurzrock, Razelle
AU - Tabernero, Josep
AU - Kononen, Juha
AU - Ng, Matthew C.H.
AU - Mehta, Rutika
AU - Uboha, Nataliya V.
AU - Bigot, Frédéric
AU - Boni, Valentina
AU - Bowyer, Samantha E.
AU - Breder, Valeriy
AU - Cervantes, Andrés
AU - Chan, Nancy
AU - Cleary, James M.
AU - Dhawan, Mallika
AU - Eefsen, Rikke L.
AU - Ewing, James
AU - Graham, Donna M.
AU - Guren, Tormod K.
AU - Kim, Jin Won
AU - Koynov, Krassimir
AU - Oh, Do Youn
AU - Redman, Rebecca
AU - Yen, Chia Jui
AU - Spetzler, David
AU - Roubaudi-Fraschini, Marie Claude
AU - Nicolas-Metral, Valerie
AU - Ait-Sarkouh, Rafik
AU - Zanna, Claudio
AU - Ennaji, Abdallah
AU - Pokorska-Bocci, Anna
AU - Flaherty, Keith T.
N1 - Publisher Copyright:
© 2024 American Association for Cancer Research.
PY - 2024/10/15
Y1 - 2024/10/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85206403252&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-24-0012
DO - 10.1158/1078-0432.CCR-24-0012
M3 - Article
C2 - 38771739
AN - SCOPUS:85206403252
SN - 1078-0432
VL - 30
SP - 4572
EP - 4583
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 20
ER -