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

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 other 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 (ORR). 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, four 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. Three of 58 evaluable patients had partial responses, representing an ORR 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.

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UNC Libraries
Published
2025-05-22
DOI
https://doi.org/10.17615/kmje-bf74
Primary Topic
Fibroblast Growth Factor Research
Type
article
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0.00

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article

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

Mallika Dhawan, Josep M. Tabernero, В. В. Бредер, Elizabeth Claire Dees et al.
UNC Libraries
Fibroblast Growth Factor Research
article

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

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

Abstract

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 other 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 (ORR). 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, four 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. Three of 58 evaluable patients had partial responses, representing an ORR 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.

UNC Libraries
University of North Carolina at Chapel Hill (US)
Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, GlaxoSmithKline, F. Hoffmann-La Roche, Merck KGaA, Mirati Therapeutics, BeiGene, Incyte, UroGen Pharma, G1 Therapeutics, Servier, Bavarian Nordic
Openalex Percentile: Top 74%
Fibroblast Growth Factor Research
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