The Evolving Role of FGFR2 Inhibitors in Intrahepatic Cholangiocarcinoma: From Molecular Biology to Clinical Targeting

Figures & data

Figure 1 Schematic representation of the FGFR signalling and other relevant oncogenic pathways in iCCA.

Table 1 Published Clinical Trials of FGFR Inhibitors in Advanced Cholangiocarcinoma

Experimental Agent	N	Study Phase	Setting	ORR %	mPFS Months	mOS Months
Infigratinib (BGJ398)^Citation51	61	II	Previously treaded advanced CCA	14.8	5.8	–
Derazantinib (ARQ087)^Citation62	29	I/II	Previously treaded advanced CCA	20.7	5.7	–
Futibatinib (TAS-120)^Citation58	67	II (FOENIX-CCA2)	Previously treaded advanced CCA	34.3	–	–
Erdafitinib^Citation59	17	II	Previously treaded advanced solid tumors and CCA	27.3	5.6	–
Pemigatinib (INCB054828)^Citation60	107	II (FIGHT-202)	Previously treaded advanced CCA	35.5	6.9	21.1
Debio 1347^Citation65	9	I (FIH)	Previously treaded solid tumors and CCA	22	–	–

Abbreviations: ORR, overall response rate; mPFS, median progression free survival; mOS, median overall survival; CCA, cholangiocarcinoma.

Table 2 Selected Ongoing Trials Evaluating FGFR Inhibitors in Advanced Cholangiocarcinoma

Treatment Arms	Study Phase	Setting	Primary End Point	Clinical Trials.gov Identifier
Pemigatinib vs gemcitabine+cisplatin	III	First Line	PFS	NCT03656536 (FIGHT-302)
Infigratinib vs gemcitabine+cisplatin	III	First Line	PFS	NCT03773302 (PROOF)
Futibatinib vs gemcitabine+cisplatin	III	First Line	PFS	NCT04093362 (FOENIX)
Derazantinib	II	After at least one prior systemic therapy	ORR and PFS at 3 months	NCT03230318
Derazantinib	II	After at least one prior systemic therapy	ORR	NCT03230318 (FIDES-01)
BGJ398 (Infigratinib)	II	After at least one prior regimen containing gemcitabine with or without cisplatin	ORR	NCT02150967
Futibatinib	II	After at least one prior systemic gemcitabine and platinum-based chemotherapy	ORR	NCT02052778
Erdafitinib	II	After at least one prior systemic therapy	ORR	NCT02699606
Erdafitinib	II	After at least one prior systemic therapy	ORR	NCT04083976
Pemigatinib	II	After at least one prior systemic therapy	ORR	NCT04256980

Abbreviations: ORR, overall response rate; PFS, progression free survival.

Sootome H, Fujioka Y, Miura A, et al. Abstract A271: TAS-120, an irreversible FGFR inhibitor, was effective in tumors harboring FGFR mutations, refractory or resistant to ATP competitive inhibitors. Mol Cancer Ther. 2013;12(11 Supplement):A271.

 Web of Science ®Google Scholar

Mazzaferro V, El-Rayes BF, Droz Dit Busset M, et al. Derazantinib (ARQ 087) in advanced or inoperable FGFR2 gene fusion-positive intrahepatic cholangiocarcinoma. Br J Cancer. 2019;120(2):165–171. doi:10.1038/s41416-018-0334-030420614

 PubMed Web of Science ®Google Scholar

Hallinan N, Finn S, Cuffe S, et al. Targeting the fibroblast growth factor receptor family in cancer. Cancer Treat Rev. 2016;46:51–62. doi:10.1016/j.ctrv.2016.03.01527109926

 PubMed Web of Science ®Google Scholar

Guagnano V, Kauffmann A, Wöhrle S, et al. FGFR genetic alterations predict for sensitivity to NVP-BGJ398, a selective pan-FGFR inhibitor. Cancer Discov. 2012;2(12):1118–1133. doi:10.1158/2159-8290.CD-12-021023002168

 PubMed Web of Science ®Google Scholar

Popiel D, Mikołajczyk A, Skupinska MM, et al. 550P preclinical characterization of CPL304110 as a potential selective inhibitor of fibroblast growth factors 1/2/3 in solid cancers. Ann Oncol. 2020;31(4):S478. doi:10.1016/j.annonc.2020.08.664

 Web of Science ®Google Scholar

Bahleda R, Italiano A, Hierro C, et al. Multicenter Phase I Study of erdafitinib (JNJ-42756493), oral pan-fibroblast growth factor receptor inhibitor, in patients with advanced or refractory solid tumors. Clin Cancer Res. 2019;25(16):4888–4897. doi:10.1158/1078-0432.CCR-18-333431088831

 PubMed Web of Science ®Google Scholar