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Lee et al. Hepatoma Res 2018;4:52 I http://dx.doi.org/10.20517/2394-5079.2018.42 Page 7 of 11

phase I first-in-human study of BLU-554 in patients with HCC (NCT02508467) is ongoing, and preliminary
results reported suggest promising clinical activity in FGF19 immunohistochemistry positive (IHC+) pa-
[68]
tients who have failed prior systemic therapy .

OTHER PROMISING FGF/FGFR INHIBITORS IN CLINICAL STUDIES
BGJ398
BGJ398 is a selective and potent pan-FGFR inhibitor which has shown to have preliminary clinical activity
in a variety of solid tumours including FGFR3-mutant bladder and urothelial cancers, FGFR1-dependent
[69]
[45]
squamous lung and head and neck cancers as well as FGFR-altered cholangiocarcinoma . Ongoing clini-
cal trials are being conducted and/or planned in the above tumour types.
AZD4547
[70]
AZD4547 is a selective FGFR1 - 3 inhibitor with activity in FGFR2-amplied gastric cancer models as well
[71]
as FGFR1-amplified NSCLC models . The randomised phase II trial in FGFR2-amplified gastric cancer did
not show an improved progression free survival for AZD4547 compared to paclitaxel though exploratory
biomarker analyses suggests that marked intratumoural heterogeneity of FGF2 amplification could have
[72]
contributed to the negative results . The phase II/III study of AZD4547 as second-line therapy in treating
FGFR-positive patients with stage IV squamous cell lung cancer is ongoing (NCT02965378).

Anti-FGFR antibodies
GP369, a monoclonal antibody against the extracellular domain of the FGFR2-IIIB receptor has shown po-
[73]
tent anti-tumour activity in breast and gastric cancer cell lines with FGFR2 amplification . MFGR1877S
(R3Mab) (NCT01363024) and B-701, both monoclonal antibodies targeting FGFR3, show promise in urothe-
lial cancers, with the latter compound being tested in combination with pembrolizumab in the second line-
setting (NCT03123055).

On the other hand, the auristatin-based antibody drug conjugate BAY 1187982 also shows significant tu-
[74]
mour growth inhibition in models of FGF2 amplified human gastric and breast cancers , which led to a
phase I dose-escalation trial in FGFR2-expressing solid tumours (NCT02368951) though the trial had to be
terminated early due to concerns over toxicity.

FGF-ligand traps
FP-1039 comprises of a soluble fusion protein consisting of extracellular FGFR1-IIIc fused to the Fc domain
of IgG1 hence acting as a ligand trap of FGF1, FGF2 and FGF4. A phase II trial is currently recruiting to
study FP-1039 alone and in combination with chemotherapy (docetaxel or paclitaxel and carboplatin) in
solid tumours (NCT01868022).

CONCLUSION
Although the majority of clinical studies with FGF/FGFR pathway inhibitors have been negative in hepato-
cellular carcinoma aside from REFLECT, the results suggest that these compounds do have anti-tumoural
activity and better biomarker-based enrichment of a target population is likely the key in planning more
[75]
successful future trials . Several ongoing clinical trials of FGF/FGFR pathway inhibitors in a biomarker-
enriched population are ongoing and we await the results of these promising studies.

DECLARATIONS
Authors’ contributions
The two authors are responsible for all the work of this article.