Advances in targeted therapy of cholangiocarcinoma

Figures & data

Figure 1. Targets and mechanisms of different drugs in cholangiocarcinoma.

Table 1. Clinical progress of FGFR inhibitors in cholangiocarcinoma.

Drug name	Disease	Stage	NCT NO.	Drug type	Indications	Experimental information	Result
Pemigatinib/INC054828	ICC	Listed	–	FGFR1/2/3 inhibitors	CCA, especially CCA of FGFR2 fusion/ rearrangement	–	–
Infigratinib/BGJ398	ICC/pCCA/dCCA	III	03773302	FGFR2 inhibitors	Advanced cholangiocarcinoma/ FGFR2 gene mutation	48 patients (Multicenter, Open Label, 2:1 Randomized, Controlled Phase 3)	–
Futibatinib/TAS120	ICC/pCCA/dCCA	II	02052778	FGFR1/2/3/4 inhibitors	Advanced cholangiocarcinoma/FGFR2 fusions/Gene rearrangement	386 patients with advanced solid tumors with and without genomic FGF/FGFR abnormalities were enrolled	Phase II clinical results are expected
Derazantinib/ARQ087	ICC/HCC	II	03230318	Pan-FGFR inhibitor	ICC/ combined HCC and CCA	148 cases of inoperable or advanced CCA with FGFR2 mutation	Phase II clinical results are expected
TT-00420	ICC/pCCA/dCCA	II	04919642	Multi-kinase inhibitors	CCA/FGFR2 fusion/FGFR2 gene mutation/FGFR1 alteration/FGFR3 alteration	80 patients with advanced/metastatic and surgically unresectable CCA	Phase II clinical results are expected
HMPL453	ICC	II	04353375	FGFR1/2/3/4 inhibitors	ICCA with FGFR2 fusion	Expect to enroll 29 patients with advanced/metastatic FGFR2 gene alteration who have failed at least one previous treatment	Phase II clinical results are expected
HH185/D185	ICC/pCCA/dCCA	II	05039892	Pan-FGFR inhibitor	FGFR2 mutant CCA	Expect to enroll 50 patients with advanced/metastatic FGFR2 gene alteration who have failed at least one previous treatment	Phase II clinical results are expected
Lenvatinib/E7080	ICC/pCCA	II	02579616/04211168	FGFR1, KIT, PDGFR and VEGFR1/2/3 inhibitors	Advanced CCA	29 patients with unresectable BTC who experienced disease progression or failure following a two-drug chemotherapy regimen with gemcitabine	ORR: 11.5% PFS:3.19 months OS:7.35 months DCR:84.6%
Gunagratinib	ICC	I / II	03758664	Pan-FGFR inhibitor	CCA resistant to first-generation FGFR inhibitors	56 patients with advanced solid tumors are expected to participate	Phase II clinical results are expected
E7090	ICC	I	04238715	FGFR1/2/3 inhibitors	CCA with FGFR2 mutations	60 patients with fusion of thecholangiocarcinoma with FGFR2 gene are expected to be enrolled.	Phase I clinical results are expected
RLY-4008	ICC	I / II	04526106	FGFR2 inhibitor	FGFR2 amplified, mutated, rearranged, translocated, and activated CCA	Expect to receive 125 patients with unresectable or unresectable metastatic ICC and other unresectable or metastatic solid tumors	Phase I clinical results are expected
Binimetinib	dCCA	II	05564403	FGFR inhibitor	Recurrent/ Unresectable dCCA	66 Patients with dCCA	–

Table 2. Clinical progress of NTRK inhibitors in cholangiocarcinoma.

Drug name	Disease	Stage	NCT NO.	Drug type	Indications	Experimental information	Result
larotrectinib	ICC	Listed	–	TRK inhibitor	Solid tumors with NTRK fusion	–	–
entrectinib	ICC/pCCA/dCCA	II	02568267	TRK/ROS inhibitors	Solid tumors with NTRK fusion	534 patients	–
selitrectinib	ICC/pCCA/dCCA	I	03215511	TRK inhibitors	Solid tumors with NTRK fusion	81 adults and children previously treated for NTRK fusion cancer	Clinical trial results are expected

Table 3. Clinical progress of IDH inhibitors in cholangiocarcinoma.

Drug name	Disease	Stage	NCT NO.	Drug type	Indications	Experimental information	Result
ivosidenib/AG-120	ICC/pCCA/dCCA	III	02989857	IDH1 inhibitor	Advanced/metastatic CCA	187 Patients with advanced cholangiocarcinoma with IDH1 mutations who had received one but not more than two systemic therapies	PFS:2.7 months vs1.4 months Other experimental results have not yet been reported
AB-218 capsule	ICC/pCCA/dCCA	I	05814536	IDH1 inhibitor	CCA with IDH1 mutation	63 Patients with IDH1 Mutation	Phase I clinical results are expected
dasatinib	ICC/pCCA/dCCA	II	02428855	IDH1 inhibitor	Advanced/metastatic CCA	8 Patients	–
enasidenib/AG-221	ICC	I/II	02273739	IDH2 inhibitor	IDH2 abnormal solid tumor	21 Adults with AITL with advanced solid tumors (including gliomas) or isocitrate dehydrogenase-2 (IDH2) mutations	–
BAY-1436032	ICC/pCCA/dCCA	I	02746081	IDH1 inhibitor	Solid tumors with abnormal IDH1	81 patients with advanced solid tumors with IDH1-R132X mutations were treated	Phase I clinical results are expected
IDH305	ICC	I	02977689	IDH1 inhibitors	Solid tumors with abnormal IDH1	The experiment has been withdrawn	–
GSK321		NOT		IDH1 inhibitors	Solid tumors with abnormal IDH1	–	–
GSK864		NOT		IDH1 inhibitors	Solid tumors with abnormal IDH1	–	–

NOT: Not entered clinical practice.

Data availability statement

Data sharing not applicable – no new data generated.