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Page 6 of 13 Pan et al. Hepatoma Res 2024;10:3 https://dx.doi.org/10.20517/2394-5079.2023.44

Table 2. FGFR inhibitor trials in patients with intrahepatic cholangiocarcinoma
Drug ClinicalTrials.gov Cohort Test population Phrase Findings
name
Pemigatinib FIGHT-202(NCT02924376) Cohort A: Pemigatinib for Previously treated locally II ORR: 35.5%
subjects with FGFR2 advanced/metastatic CCA DCR: 82%
translocation and harboring FGFR2 median PFS: 6.9
documented fusion partner. fusions/rearrangements months (95%CI:
Cohort B: Pemigatinib for 6.2 to 9.6)
subjects with other median OS: 21.1
FGF/FGFR alterations. months (95%CI:
Cohort C: Pemigatinib for 14.8 to Not
subjects without FGF/FGFR estimable)
alterations.
FIGHT-302(NCT02924376) Experimental: Pemigatinib Advanced ICC harboring FGFR2 III recruiting
Active Comparator: rearrangements
Gemcitabine + Cisplatin
Infigratinib CBGJ398X2204(NCT02150967) Experimental: BGJ398 Advanced/metastatic II ORR: 23.1%
(infigratinib) cholangiocarcinoma with FGFR2 (95%CI: 15.6% to
translocations 32.2%)
DCR: 84.3%
(95%CI: 76.0% to
90.6%)
median PFS: 7.3
months (95%CI:
5.6 to 7.6)
median OS: 12.2
months (95%CI:
10.7 to 14.9)
Futibatinib FOENIX-CCA4 (NCT05727176) Experimental: Futibatinib Advanced ICC FGFR2 II ORR: 41.7%
rearrangements median PFS: 8.9
months
12-month OS:
73.1%
DCR: 82.5%
DOR: 9.5 months
12-month RFS:
35.4%
median OS: 20.0
months
Derazantinib FIDES-01(NCT03230318) Experimental: derazantinib Advanced ICC FGFR2 fusions, II ORR: 21.4%
rearrangements, or amplification (95%CI: 13.9% to
30.5%)
DCR: 75.7%
(95%CI: 66.3% to
83.6%)
median PFS: 8.0
months (95%CI:
5.5 to 8.3)
median OS: 15.9
months (95%CI:
12.5 to 22.6)

The combination of conventional chemotherapy and trastuzumab has also exhibited effectiveness. In a
phase II trial carried out in Korea, assessing the use of FOLFOX alongside trastuzumab in individuals
[48]
diagnosed with HER2-positive conditions, the therapeutic regimen yielded a 29.4% ORR .

BRAF proto-oncogene inhibitors
[49]
BRAF, a proto-oncogene, exerts a pivotal role in the regulation of cell processes . While BRAF mutations
are rare in advanced BTC, accounting for only 1%-5% of actionable findings, they are more prevalent in
ICC . Specifically, the BRAF V600E mutation in ICC accounts for 27% of the identified BRAF variants,
[27]
which leads to activation of the MAPK/ERK signaling pathway, causing uncontrolled cell proliferation and
[49]
contributing to tumor progression .