BACKGROUND: Prognosis of patients affected by metastatic esophageal-gastric 
junction (EGJ) or gastric cancer (GC) remains dismal. Trastuzumab, an anti-HER2 
monoclonal antibody, is the only targeted agent approved for the first-line 
treatment of patients with HER2-overexpressing advanced EGJ or GC in combination 
with chemotherapy. However, patients invariably become resistant during this 
treatment. We recently identified the overexpression of fibroblast growth factor 
(FGF) receptor 3 (FGFR3) as a molecular mechanism responsible for trastuzumab 
resistance in GC models, providing the rationale for the inhibition of this 
receptor as a potential second-line strategy in this disease. Pemigatinib is a 
selective, potent, oral inhibitor of FGFR1, 2, and 3.
METHODS: The FiGhTeR trial is a phase II, single-arm, open-label study to assess 
safety and activity of the FGFR inhibitor pemigatinib as second-line treatment 
strategy in metastatic EGJ/GC patients progressing under trastuzumab-containing 
therapies. The primary endpoint is the 12-week progression-free survival rate. 
Plasma and tumor tissue samples will be collected for translational research 
analyses at baseline, during treatment, and at progression on pemigatinib.
DISCUSSION: Co-alterations in genes coding for different tyrosine-kinase 
receptors are emerging as relevant mechanisms of acquired resistance to 
anti-HER2 therapeutic strategies in GC. In particular, our group has recently 
identified that in GC models the overexpression of FGFR3 sustains the acquired 
resistance to trastuzumab. This trial aims to assess the safety, tolerability 
and activity of the FGFR inhibitor pemigatinib as a second-line treatment in 
metastatic EGJ/GC patients refractory to first-line trastuzumab-containing 
therapies. Furthermore, this study offers the opportunity to prospectively study 
mechanisms and pathways involved in trastuzumab resistance.
PROTOCOL NUMBER: CRC2017_02.
EUDRACT NUMBER: 2017-004522-14.