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Clin Cancer Res. 2019 May 1;25(9):2699-2707. doi: 10.1158/1078-0432.CCR-18-1959. Epub 2019 Feb 11.

A Phase I, Open-Label, Multicenter, Dose-escalation Study of the Oral Selective FGFR Inhibitor Debio 1347 in Patients with Advanced Solid Tumors Harboring FGFR Gene Alterations.

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Memorial Sloan Kettering Cancer Center, New York, New York.
Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
Massachusetts General Hospital Cancer Center, Boston, Massachusetts.
Dana-Farber Cancer Institute, Boston, Massachusetts.
The University of Texas MD Anderson Cancer Center, Houston, Texas.
Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, New York.
Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
Debiopharm International SA, Lausanne, Switzerland.
Memorial Sloan Kettering Cancer Center, New York, New York.



To investigate tolerability, efficacy, and pharmacokinetics/pharmacodynamics of Debio 1347, a selective FGFR inhibitor.


This was a first-in-human, multicenter, open-label study in patients with advanced solid tumors harboring FGFR1-3 gene alterations. Eligible patients received oral Debio 1347 at escalating doses once daily until disease progression or intolerable toxicity. Dose-limiting toxicities (DLT) were evaluated during the first 4 weeks on treatment, pharmacokinetics/pharmacodynamics postfirst dose and after 4 weeks.


A total of 71 patients were screened and 58 treated with Debio 1347 at doses from 10 to 150 mg/day. Predominant tumor types were breast and biliary duct cancer, most common gene alterations were FGFR1 amplifications (40%) and mutations in FGFR2 (12%) and FGFR3 (17%); 12 patients (21%) showed FGFR fusions. Five patients at three dose levels had six DLTs (dry mouth/eyes, hyperamylasemia, hypercalcemia, hyperbilirubinemia, hyperphosphatemia, and stomatitis). The maximum tolerated dose was not reached, but dermatologic toxicity became sometimes dose limiting beyond the DLT period at ≥80 mg/day. Adverse events required dose modifications in 52% of patients, mostly due to dose-dependent, asymptomatic hyperphosphatemia (22%). RECIST responses were seen across tumor types and mechanisms of FGFR activation. Six patients, 3 with FGFR fusions, demonstrated partial responses, 10 additional patients' tumor size regressions of ≤30%. Plasma half-life was 11.5 hours. Serum phosphate increased with Debio 1347 plasma levels and confirmed target engagement at doses ≥60 mg/day.


Preliminary efficacy was encouraging and tolerability acceptable up to 80 mg/day, which is now used in an extension part of the study.

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