Faculty, Staff and Student Publications

Publication Date

10-15-2024

Journal

Clinical Cancer Research

DOI

10.1158/1078-0432.CCR-24-0012

PMID

38771739

PMCID

PMC11707795

PubMedCentral® Posted Date

1-8-2025

PubMedCentral® Full Text Version

Author MSS

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 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.

Keywords

Humans, Female, Male, Middle Aged, Aged, Neoplasms, Adult, Oncogene Proteins, Fusion, Aged, 80 and over, Receptor, Fibroblast Growth Factor, Type 1, Receptor, Fibroblast Growth Factor, Type 3, Treatment Outcome, Protein Kinase Inhibitors, basket trial, Debio 1347, fibroblast growth factor receptor, FUZE, gene fusion, molecular profiling

Published Open-Access

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