Related Experiment Video
Updated: May 13, 2026
Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Evaluating Debio 1347 in Patients with FGFR Fusion-Positive Advanced Solid Tumors from the FUZE Multicenter,
Petros Grivas1, Elena Garralda2, Funda Meric-Bernstam3
1Division of Hematology/Oncology, Department of Medicine, University of Washington, Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington.
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. See related commentary by Hage Chehade et al., p. 4549.
Insights
This study found that Debio 1347, an FGFR inhibitor, showed limited efficacy in patients with solid tumors harboring FGFR fusions, despite manageable toxicity. Further clinical evaluation is not supported.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Fibroblast Growth Factor Receptor (FGFR) fusions are implicated in various solid tumors.
- Targeting FGFR with small molecule inhibitors is a therapeutic strategy for these cancers.
Purpose of the Study:
- To investigate the efficacy, safety, and pharmacokinetics of Debio 1347, a selective FGFR1-3 inhibitor.
- To evaluate Debio 1347 in patients with solid tumors harboring functional FGFR1-3 fusions.
Main Methods:
- A multicenter phase II basket trial enrolled adult patients with previously treated advanced biliary tract, urothelial, or other solid tumors with FGFR fusions.
- Debio 1347 was administered orally at 80 mg once daily.
- Primary endpoint was objective response rate; secondary endpoints included duration of response, progression-free survival, overall survival, and safety.
Main Results:
- The trial enrolled 63 patients; 58 were evaluable. An objective response rate of 5% (3 partial responses) was observed, with 45% stable disease.
- Grade ≥3 treatment-related adverse events occurred in 35% of patients, most commonly hyperphosphatemia (13%) and stomatitis (5%).
- Two patients (3%) discontinued treatment due to adverse events.
Conclusions:
- Debio 1347 demonstrated manageable toxicity in patients with FGFR-fusion-positive solid tumors.
- The observed efficacy did not support further clinical development of Debio 1347 in this patient population.
- Transcriptomic analysis detailed FGFR fusion incidence across solid tumors.
![An Automated Radiosynthesis of [68Ga]Ga-FAPI-46 for Routine Clinical Use](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F66708.jpg&w=3840&q=50)
