Phase I study of the irreversible fibroblast growth factor receptor 1-4 inhibitor futibatinib in Japanese patients with advanced solid tumors.
Cancer Sci
; 114(2): 574-585, 2023 Feb.
Article
em En
| MEDLINE
| ID: mdl-35838190
ABSTRACT
This phase I study was designed to (1) determine the maximum tolerated dose (MTD) and recommended dose (RD) of the fibroblast growth factor receptor (FGFR) inhibitor futibatinib in Japanese patients with advanced solid tumors, and (2) examine the antitumor activity of the RD in patients with gastric cancer (GC) or other advanced solid tumors who have FGFR or FGF/FGFR abnormalities, respectively. In the dose-escalation phase, patients were assigned to 21-day cycles of oral futibatinib 8-160 mg three times a week (TIW) or 16 or 20 mg once daily (QD). In the expansion phase, patients received oral futibatinib 56, 80, or 120 mg TIW, or 16 or 20 mg QD. Eighty-three patients received futibatinib TIW (n = 40) or QD (n = 43). No dose-limiting toxicities were observed according to the final study protocol definition, and the MTD was not reached. The most common adverse events with both regimens were hyperphosphatemia (TIW, 82.5%; QD, 100.0%) and decreased appetite (TIW, 40.0%; QD, 58.1%). Hyperphosphatemia was asymptomatic, not leading to futibatinib discontinuation. The overall response rate (ORR) was 11.5% in patients with FGF/FGFR abnormalities. Notably, in GC patients harboring FGFR2 copy number (CN) ≥10, the ORR was 36.4% versus 0 in patients with CN <10. Therefore, futibatinib had a generally predictable and manageable safety profile in patients with advanced solid tumors. Antitumor activity was seen in patients with FGF/FGFR abnormalities, particularly those with GC and high FGFR2 CNs. Thus, futibatinib 20 mg QD was chosen as the RD for phase II studies.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
/
Inibidores de Proteínas Quinases
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Cancer Sci
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Japão