Intrahepatic cholangiocarcinoma

Summary

Intrahepatic cholangiocarcinoma (MONDO:0003210) is a disease (an umbrella term covering 6 Mondo subtypes) with 5 cohort genes and 192 clinical trials. Molecularly, FGFR2::v Fusion OR FGFR2::? Fusion confers sensitivity to Futibatinib in Intrahepatic Cholangiocarcinoma (CIViC Level A); 8 further subtype–drug associations are mapped below. Top therapeutic interventions include lenvatinib, floxuridine, and pemigatinib.

At a glance

• Umbrella term: 6 Mondo subtypes
• Cohort genes: 5
• ClinVar variants: 3
• Clinical trials: 192
• Precision-medicine evidence (CIViC): 9 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intrahepatic cholangiocarcinoma
Mondo ID	MONDO:0003210
EFO	EFO:1001961
DOID	DOID:4928
ICD-10-CM	C22.1
ICD-11	1253728223, 387909164
NCIT	C35417
SNOMED CT	109842005
UMLS	C0345905
MedGen	87521
GARD	0006042
Is cancer (heuristic)	no

Also known as: cholangiocarcinoma, intrahepatic, malignant · ICC · IHCH · intrahepatic bile duct cancer (cholangiocarcinoma) · intrahepatic bile duct carcinoma · intrahepatic carcinoma of bile duct · intrahepatic carcinoma of the bile duct · intrahepatic cholangiocarcinoma · intrahepatic cholangiocarcinoma (bile duct cancer) · intrahepatic Cholangiocellular carcinoma

Data availability: 3 ClinVar variants · 90 cell lines.

Disease family

An umbrella term covering 6 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › digestive system cancer › liver cancer › biliary tract cancer › bile duct cancer › intrahepatic bile duct cancer › intrahepatic cholangiocarcinoma

Related subtypes (1): intrahepatic bile duct adenosquamous carcinoma

Subtypes (6): hilar cholangiocarcinoma, mucinous intrahepatic cholangiocarcinoma, cholangiolocellular carcinoma, signet ring cell intrahepatic cholangiocarcinoma, sarcomatous intrahepatic cholangiocarcinoma, perihilar intrahepatic cholangiocarcinoma

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

3 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
133537	NM_000038.6(APC):c.8332G>T (p.Ala2778Ser)	APC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
482375	NM_000038.6(APC):c.4440G>C (p.Gln1480His)	APC	Uncertain significance	criteria provided, multiple submitters, no conflicts
559959	NM_000038.6(APC):c.8461G>A (p.Asp2821Asn)	APC	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 52 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BRAF	Orphanet:1340	Cardiofaciocutaneous syndrome
BRAF	Orphanet:146	Differentiated thyroid carcinoma
BRAF	Orphanet:251615	Pilomyxoid astrocytoma
BRAF	Orphanet:389	Langerhans cell histiocytosis
BRAF	Orphanet:500	Noonan syndrome with multiple lentigines
BRAF	Orphanet:54595	Craniopharyngioma
BRAF	Orphanet:58017	Classic hairy cell leukemia
BRAF	Orphanet:626	Large/giant congenital melanocytic nevus
BRAF	Orphanet:648	Noonan syndrome
BRAF	Orphanet:840	Syringocystadenoma papilliferum
BRAF	Orphanet:96253	Cushing disease
TP53	Orphanet:1333	Familial pancreatic carcinoma
TP53	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
TP53	Orphanet:1501	Adrenocortical carcinoma
TP53	Orphanet:210159	Adult hepatocellular carcinoma
TP53	Orphanet:251576	Gliosarcoma
TP53	Orphanet:251579	Giant cell glioblastoma
TP53	Orphanet:251899	Choroid plexus carcinoma
TP53	Orphanet:2807	Papilloma of choroid plexus
TP53	Orphanet:293199	Pleomorphic rhabdomyosarcoma
TP53	Orphanet:3318	Essential thrombocythemia
TP53	Orphanet:524	Li-Fraumeni syndrome
TP53	Orphanet:52688	Myelodysplastic syndrome
TP53	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
TP53	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
TP53	Orphanet:668	Osteosarcoma
TP53	Orphanet:67038	B-cell chronic lymphocytic leukemia
TP53	Orphanet:70573	Small cell lung cancer
TP53	Orphanet:96253	Cushing disease
TP53	Orphanet:99756	Alveolar rhabdomyosarcoma
TP53	Orphanet:99757	Embryonal rhabdomyosarcoma
GNAS	Orphanet:189427	Cushing syndrome due to bilateral macronodular adrenocortical disease
GNAS	Orphanet:2762	Progressive osseous heteroplasia
GNAS	Orphanet:562	McCune-Albright syndrome
GNAS	Orphanet:57782	Mazabraud syndrome
GNAS	Orphanet:79443	Pseudohypoparathyroidism type 1A
GNAS	Orphanet:79444	Pseudohypoparathyroidism type 1C
GNAS	Orphanet:79445	Pseudopseudohypoparathyroidism
GNAS	Orphanet:93276	Polyostotic fibrous dysplasia
GNAS	Orphanet:93277	Monostotic fibrous dysplasia
GNAS	Orphanet:94089	Pseudohypoparathyroidism type 1B
IDH1	Orphanet:163634	Maffucci syndrome
IDH1	Orphanet:251576	Gliosarcoma
IDH1	Orphanet:251579	Giant cell glioblastoma
IDH1	Orphanet:296	Ollier disease
IDH1	Orphanet:86845	Acute myeloid leukaemia with myelodysplasia-related features
IDH1	Orphanet:99646	Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria
APC	Orphanet:220460	Attenuated familial adenomatous polyposis
APC	Orphanet:261584	5q22 microdeletion syndrome
APC	Orphanet:314022	Gastric adenocarcinoma and proximal polyposis of the stomach

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	4
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	civic_evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	civic_evidence
GNAS	HGNC:4392	ENSG00000087460	O95467	Neuroendocrine secretory protein 55	civic_evidence
IDH1	HGNC:5382	ENSG00000138413	O75874	Isocitrate dehydrogenase [NADP] cytoplasmic	civic_evidence
APC	HGNC:583	ENSG00000134982	P25054	Adenomatous polyposis coli protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
IDH1	Isocitrate dehydrogenase [NADP] cytoplasmic	Catalyzes the NADP(+)-dependent oxidative decarboxylation of isocitrate (D-threo-isocitrate) to 2-ketoglutarate (2-oxoglutarate), which is required by other enzymes such as the phytanoyl-CoA dioxygenase.
APC	Adenomatous polyposis coli protein	Tumor suppressor.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.4

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	1	5.5×	0.634
Enzyme (other)	1	2.4×	0.634
Transcription factor	1	1.6×	0.634
Other/Unknown	2	0.7×	0.877

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
GNAS	Other/Unknown	no		NESP55, Gprotein_alpha_S, Gprotein_alpha_su
IDH1	Enzyme (other)	yes	1.1.1.42	Isocitrate_DH_NADP, IsoCit/isopropylmalate_DH_CS, IsoPropMal-DH-like_dom
APC	Other/Unknown	no		Armadillo, APC_rpt, SAMP

Expression context

Cohort genes with no expression data: 0.

5 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
calcaneal tendon	1
colonic epithelium	1
ganglionic eminence	1
tendon of biceps brachii	1
ventricular zone	1
Brodmann (1909) area 46	1
postcentral gyrus	1
type B pancreatic cell	1
adrenal tissue	1
corpus epididymis	1
jejunal mucosa	1
medial globus pallidus	1
substantia nigra pars compacta	1
substantia nigra pars reticulata	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
GNAS	312	ubiquitous	marker	type B pancreatic cell, postcentral gyrus, Brodmann (1909) area 46
IDH1	294	ubiquitous	marker	corpus epididymis, jejunal mucosa, adrenal tissue
APC	297	ubiquitous	marker	substantia nigra pars compacta, substantia nigra pars reticulata, medial globus pallidus

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
BRAF	7,394
IDH1	5,464
APC	2,903
GNAS	410

Intra-cohort edges

A	B	Sources
BRAF	TP53	string_interaction
IDH1	TP53	string_interaction

Structural data

PDB: 5 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GNAS	O95467	490
TP53	P04637	313
BRAF	P15056	131
IDH1	O75874	61
APC	P25054	31

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 130. Enrichment computed across 5 evidence-associated genes (5 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate	1	2284.0×	0.014	IDH1
APC truncation mutants are not K63 polyubiquitinated	1	2284.0×	0.014	APC
Loss of function of TP53 in cancer due to loss of tetramerization ability	1	2284.0×	0.014	TP53
Ovarian tumor domain proteases	2	111.4×	0.014	TP53, APC
NADPH regeneration	1	1142.0×	0.019	IDH1
Regulation of TP53 Expression	1	1142.0×	0.019	TP53
NFE2L2 regulating TCA cycle genes	1	761.3×	0.020	IDH1
Transcriptional activation of cell cycle inhibitor p21	1	571.0×	0.020	TP53
Signaling by MRAS-complex mutants	1	571.0×	0.020	BRAF
Signalling to p38 via RIT and RIN	1	456.8×	0.020	BRAF
Activation of NOXA and translocation to mitochondria	1	380.7×	0.020	TP53
Negative feedback regulation of MAPK pathway	1	380.7×	0.020	BRAF
ARMS-mediated activation	1	326.3×	0.020	BRAF
RUNX3 regulates CDKN1A transcription	1	326.3×	0.020	TP53
Prolonged ERK activation events	1	285.5×	0.020	BRAF
SHOC2 M1731 mutant abolishes MRAS complex function	1	285.5×	0.020	BRAF
Gain-of-function MRAS complexes activate RAF signaling	1	285.5×	0.020	BRAF
PI5P Regulates TP53 Acetylation	1	253.8×	0.020	TP53
Activation of PUMA and translocation to mitochondria	1	228.4×	0.020	TP53
Signaling by FGFR3	1	228.4×	0.020	BRAF
Signaling by AXIN mutants	1	207.6×	0.020	APC
Signaling by CTNNB1 phospho-site mutants	1	207.6×	0.020	APC
Signaling by APC mutants	1	207.6×	0.020	APC
Signaling by AMER1 mutants	1	207.6×	0.020	APC
Signaling by FGFR4	1	207.6×	0.020	BRAF
Frs2-mediated activation	1	190.3×	0.020	BRAF
TP53 Regulates Transcription of Caspase Activators and Caspases	1	190.3×	0.020	TP53
TP53 Regulates Transcription of Death Receptors and Ligands	1	190.3×	0.020	TP53
Urea cycle	1	175.7×	0.020	TP53
APC truncation mutants have impaired AXIN binding	1	163.1×	0.020	APC

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of helicase activity	1	3370.4×	0.009	TP53
regulation of phospholipid catabolic process	1	3370.4×	0.009	IDH1
cellular response to actinomycin D	1	3370.4×	0.009	TP53
regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1	3370.4×	0.009	TP53
negative regulation of G1 to G0 transition	1	3370.4×	0.009	TP53
glyoxylate cycle	1	1685.2×	0.009	IDH1
positive regulation of mitochondrial membrane permeability	1	1685.2×	0.009	TP53
regulation of phospholipid biosynthetic process	1	1685.2×	0.009	IDH1
oligodendrocyte apoptotic process	1	1685.2×	0.009	TP53
negative regulation of glucose catabolic process to lactate via pyruvate	1	1685.2×	0.009	TP53
negative regulation of pentose-phosphate shunt	1	1685.2×	0.009	TP53
obsolete homolactic fermentation	1	1123.5×	0.009	TP53
adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway	1	1123.5×	0.009	GNAS
CD4-positive or CD8-positive, alpha-beta T cell lineage commitment	1	1123.5×	0.009	BRAF
signal transduction by p53 class mediator	1	1123.5×	0.009	TP53
negative regulation of miRNA processing	1	1123.5×	0.009	TP53
intrinsic apoptotic signaling pathway in response to hypoxia	1	1123.5×	0.009	TP53
regulation of fibroblast apoptotic process	1	1123.5×	0.009	TP53
T cell proliferation involved in immune response	1	842.6×	0.009	TP53
positive regulation of programmed necrotic cell death	1	842.6×	0.009	TP53
response to parathyroid hormone	1	842.6×	0.009	GNAS
oxidative stress-induced premature senescence	1	842.6×	0.009	TP53
B cell lineage commitment	1	674.1×	0.009	TP53
T cell lineage commitment	1	674.1×	0.009	TP53
isocitrate metabolic process	1	674.1×	0.009	IDH1
NADPH regeneration	1	674.1×	0.009	IDH1
adenylate cyclase-activating serotonin receptor signaling pathway	1	674.1×	0.009	GNAS
mRNA transcription	1	674.1×	0.009	TP53
positive regulation of RNA polymerase II transcription preinitiation complex assembly	1	674.1×	0.009	TP53
positive regulation of axon regeneration	1	674.1×	0.009	BRAF

Therapeutics

Drugs indicated for this disease

0 approved, 11 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Bortezomib	Phase 3 (in late-stage trials)
Capecitabine	Phase 3 (in late-stage trials)
Carboplatin	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Fluorouracil	Phase 3 (in late-stage trials)
Gemcitabine	Phase 3 (in late-stage trials)
Irinotecan	Phase 3 (in late-stage trials)
Lenvatinib	Phase 3 (in late-stage trials)
Oxaliplatin	Phase 3 (in late-stage trials)
Tislelizumab	Phase 3 (in late-stage trials)
Toripalimab	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Adebrelimab, Atezolizumab, Bevacizumab, Bintrafusp Alfa, Cabozantinib, Cadonilimab, Camrelizumab, Dexamethasone, Durvalumab, Famitinib, Floxuridine, Paclitaxel, Perflutren, Ramucirumab, Regorafenib, Rivoceranib, Sintilimab, Surufatinib, Tremelimumab.

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 2

Druggability breadth: 5 of 5 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
BRAF	VEMURAFENIB
TP53	NITROFURANTOIN
IDH1	ENASIDENIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
BRAF	48	4
IDH1	10	4
GNAS	0	0
APC	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VEMURAFENIB	4	BRAF
PONATINIB	4	BRAF
FEDRATINIB	4	BRAF
SORAFENIB	4	BRAF
DASATINIB ANHYDROUS	4	BRAF
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF
INFIGRATINIB	4	BRAF
REGORAFENIB	4	BRAF
DABRAFENIB	4	BRAF
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF
ABEMACICLIB	4	BRAF
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF
PAZOPANIB	4	BRAF
DASATINIB	4	BRAF
ERLOTINIB	4	BRAF
GEFITINIB	4	BRAF
IMATINIB	4	BRAF
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
IDH1	488	Binding:475, Functional:12, ADMET:1
APC	24	Binding:24

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BRAF	2.7.10.2, 2.7.11.1	non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
IDH1	1.1.1.42	isocitrate dehydrogenase (NADP+)

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
BRAF	1,442
TP53	869
IDH1	488

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

28 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
VEMURAFENIB	4	BRAF
PONATINIB	4	BRAF
FEDRATINIB	4	BRAF
SORAFENIB	4	BRAF
DASATINIB ANHYDROUS	4	BRAF
RUXOLITINIB	4	BRAF
INFIGRATINIB	4	BRAF
REGORAFENIB	4	BRAF
DABRAFENIB	4	BRAF
NILOTINIB	4	BRAF
ABEMACICLIB	4	BRAF
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF
PAZOPANIB	4	BRAF
DASATINIB	4	BRAF
ERLOTINIB	4	BRAF
GEFITINIB	4	BRAF
IMATINIB	4	BRAF
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	BRAF, TP53, IDH1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	GNAS, APC

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
GNAS	0	—
APC	24	—

Clinical trials & evidence

Clinical trials

Clinical trials: 192.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	100
Not specified	52
PHASE1	14
PHASE3	9
PHASE1/PHASE2	9
PHASE2/PHASE3	4
EARLY_PHASE1	3
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06417606	PHASE4	NOT_YET_RECRUITING	Lenvatinib and Adebrelimab Combined With GEMOX in the Perioperative Treatment of Potentially Resectable Intrahepatic Cholangiocarcinoma
NCT04353375	PHASE2/PHASE3	RECRUITING	HMPL-453 Tartrate in Advanced Intrahepatic Cholangiocarcinoma
NCT04669496	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Phase II-III Clinical Trial of PD1 Antibody (Toripalimab), Lenvatinib and GEMOX Neoadjuvant Treatment for Resectable Intrahepatic Cholangiocarcinoma With High-risk Recurrence Factors
NCT05342194	PHASE3	RECRUITING	Toripalimab Plus Lenvatinib and Gemcitabine-based Chemotherapy in 1L Treatment of Advanced ICC: a Phase III Study
NCT07328919	PHASE3	NOT_YET_RECRUITING	Efficacy and Safety of TT-00420 (Tinengotinib) Tablets Versus Chemotherapy in Patients With Advanced Intrahepatic Cholangiocarcinoma Harboring FGFR2 Fusions/Rearrangements or Mutations
NCT02200042	PHASE3	TERMINATED	Radiation Therapy vs. Observation Following Gemcitabine and Cisplatin for Inoperable Localized Liver Cancer
NCT02807181	PHASE2/PHASE3	TERMINATED	SIRT Followed by CIS-GEM Chemotherapy Versus CIS-GEM Chemotherapy Alone as 1st Line Treatment of Patients With Unresectable Intrahepatic Cholangiocarcinoma
NCT03081039	PHASE3	WITHDRAWN	A Study of Cisplatin or Carboplatin With Gemcitabine Versus Gemcitabine Alone as Adjuvant Therapy in Patients With Resected or Ablation Intra-Hepatic Cholangiocarcinoma
NCT03086993	PHASE2/PHASE3	UNKNOWN	Percutaneous Hepatic Perfusion vs. Cisplatin/Gemcitabine in Patients With Intrahepatic Cholangiocarcinoma
NCT03345303	PHASE3	UNKNOWN	Bortezomib in Intrahepatic Cholangiocellular Carcinoma
NCT03768414	PHASE3	COMPLETED	Gemcitabine Hydrochloride and Cisplatin With or Without Nab-Paclitaxel in Treating Patients With Newly Diagnosed Advanced Biliary Tract Cancers
NCT03771846	PHASE3	UNKNOWN	HAIC Versus Systemic Chemotherapy for Unresectable ICC
NCT03940378	PHASE3	UNKNOWN	Treatment of Advanced Intrahepatic Cholangiocarcinoma
NCT04961970	PHASE3	UNKNOWN	HAIC With FOLFOX Versus Systemic Chemotherapy With GP for Unresectable ICC
NCT02834013	PHASE2	ACTIVE_NOT_RECRUITING	Nivolumab and Ipilimumab in Treating Patients With Rare Tumors
NCT03942328	PHASE1/PHASE2	RECRUITING	Modified Immune Cells (Autologous Dendritic Cells) and a Vaccine (Prevnar) Combined With Immune Checkpoint Inhibition After High-Dose External Beam Radiation Therapy in Treating Patients With Unresectable Liver Cancer
NCT04175912	PHASE2	ACTIVE_NOT_RECRUITING	Testing the Combination of Pevonedistat With Chemotherapy for Bile Duct Cancer of the Liver
NCT04238637	PHASE2	ACTIVE_NOT_RECRUITING	Immunotherapy Combined With Y-90 SIRT Therapy in Advanced Stage Intrahepatic Biliary Tract Cancer (BTC)
NCT04251715	PHASE2	ACTIVE_NOT_RECRUITING	mFOLFIRINOX Followed by Hepatic Arterial Infusion of Floxuridine and Dexamethasone With Systemic mFOLFIRI for Unresectable Liver-dominant Intrahepatic Cholangiocarcinoma
NCT04295317	PHASE2	ACTIVE_NOT_RECRUITING	PD-1 Antibody (SHR-1210) Plus Capecitabine in Patients with Intrahepatic Cholangiocarcinoma After Surgery
NCT04299581	PHASE2	RECRUITING	Cryoablation Combined with Anti-PD-1 Antibody in Patients with Advanced Intrahepatic Cholangiocarcinoma
NCT04891289	PHASE2	RECRUITING	Gemcitabine and Oxaliplatin Chemotherapy With or Without a Floxuridine and Dexamethasone Pump in People With Cholangiocarcinoma That Cannot Be Removed With Surgery
NCT04941287	PHASE2	ACTIVE_NOT_RECRUITING	Testing A New Combination of Anti-cancer Immune Therapies, Atezolizumab and CDX-1127 (Varlilumab) With or Without the Addition of a Third Anti-cancer Drug, Cobimetinib, for Advanced-Stage Biliary Tract Cancer
NCT04954781	PHASE2	RECRUITING	TACE Combined With Tislelizumab in Patients With Advanced Intrahepatic Cholangiocarcinoma
NCT05010681	PHASE2	RECRUITING	Lenvatinib Plus Sintilimab in Patients With Immune Checkpoint Inhibitor Previously Treated Advanced Liver Cancer
NCT05174650	PHASE2	ACTIVE_NOT_RECRUITING	Treatment of Atezolizumab and Derazantinib in Patients With Advanced iCCA With FGFR2 Fusions/Rearrangements
NCT05223816	PHASE2	RECRUITING	An Open-Label, Multiple-Center, Phase IIa/IIb Clinical Trial to Evaluate the Efficacy, Safety and Tolerability of VG161 as Monotherapy and in Combination With Nivolumab for Treatment of Patients With Hepatocellular Carcinoma or Intrahepatic Cholangiocarcinoma
NCT05286814	PHASE2	RECRUITING	PDS01ADC in Combination With Hepatic Artery Infusion Pump (HAIP) and Systemic Therapy for Subjects With Metastatic Colorectal Cancer, Intrahepatic Cholangiocarcinoma, or Metastatic Adrenocortical Carcinoma
NCT05422690	PHASE2	RECRUITING	The Purpose of This Research Study is to See if Combining Gemcitabine, Cisplatin and Durvalumab Chemotherapy Treatments With a Direct Tumor Therapy Yittrium-90 (Y-90) Will Work Better Together to Shrink Tumors and Control Cancer
NCT05557578	PHASE2	RECRUITING	GOT Applied As Neoadjuvant Regimen for Patients of Resectable ICC with High-risk Factors of Recurrence
NCT05564403	PHASE2	ACTIVE_NOT_RECRUITING	Study of Chemotherapy, With or Without Binimetinib in Advanced Biliary Tract Cancers in 2nd Line Setting (A ComboMATCH Treatment Trial)
NCT05655949	PHASE2	RECRUITING	Y-90 With Durvalumab/Gem/Cis in Intrahepatic Cholangio
NCT05678270	PHASE2	RECRUITING	A Study of ICP-192 in Patients With FGFR2-Rearranged Unresectable or Metastatic Intrahepatic Cholangiocarcinoma
NCT06178588	PHASE2	ACTIVE_NOT_RECRUITING	Sacituzumab Govitecan for the Treatment for Patients With Locally Advanced, Recurrent, or Metastatic Cholangiocarcinoma
NCT06208462	PHASE2	RECRUITING	Neoadjuvant Therapy of HAIC（GEMOX） Combined With Adebrelimab and Lenvatinib for Resectable Intrahepatic Cholangiocarcinoma With High-risk Recurrence Factors
NCT06239532	PHASE2	ACTIVE_NOT_RECRUITING	HAIC Sequential TAE Combined With Tislelizumab and Surufatinib in Unresectable Intrahepatic Cholangiocarcinoma
NCT06296563	PHASE2	RECRUITING	Perioperative Treatment of Resectable Intrahepatic Cholangiocarcinoma With the Combination of Adebrelimab and Apatinib and HAIC
NCT06298968	PHASE2	RECRUITING	Combined Therapy Using Gemcitabine and Cisplatin Chemotherapy, Lenvatinib and Adebrelimab for Patients With Advanced and Unresectable Intrahepatic Cholangiocarcinoma
NCT06313203	PHASE2	RECRUITING	HAI-Floxuridine, or SIRT, Combined With Gemox For Patients With Intra-Hepatic Cholangiocarcinoma Not Amenable to Resection (TOMCAT)
NCT06375642	PHASE2	NOT_YET_RECRUITING	A Single Arm, Single Centered Phase II Trial on the Combination of Adebrelimab, Surufatinib and Irinotecan Liposome-based HAIC in Advanced iCC

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LENVATINIB	4	16
FLOXURIDINE	4	6
PEMIGATINIB	4	3
COBIMETINIB	4	2
GEMCITABINE	4	2
BINIMETINIB	4	1
BORTEZOMIB	4	1
CABOZANTINIB	4	1
CALCITRIOL	4	1
CHLOROTRIANISENE	4	1
ENASIDENIB	4	1
INFIGRATINIB PHOSPHATE	4	1
LEVAMISOLE HYDROCHLORIDE	4	1
MELPHALAN	4	1
PERFLUTREN	4	1
RAMUCIRUMAB	4	1
SACITUZUMAB GOVITECAN	4	1
TECHNETIUM TC 99M SULFUR COLLOID	4	1
TEGAFUR	4	1
TORIPALIMAB	4	1
SINTILIMAB	3	8
ADEBRELIMAB	3	5
FAMITINIB	3	2
SURUFATINIB	3	2
BINTRAFUSP ALFA	3	1
CATEQUENTINIB HYDROCHLORIDE	3	1
CM-4307	3	1
ENLONSTOBART	3	1
GUADECITABINE	3	1
PEVONEDISTAT	3	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 9 predictive associations from 10 curated evidence items; also 1 prognostic.

Molecular subtype	Therapy	Effect	Level	CIViC
FGFR2::v Fusion OR FGFR2::? Fusion	Futibatinib	Sensitivity/Response	CIViC A	EID11609 +1
FGFR2::BICC1 Fusion	Futibatinib	Sensitivity/Response	CIViC B	EID11610
FGFR2::v Fusion OR FGFR2::? Fusion	Derazantinib	Sensitivity/Response	CIViC B	EID7329
BRAF V600E	Dabrafenib + Trametinib	Sensitivity/Response	CIViC C	EID5903
BRAF V600E	Trametinib + Dabrafenib	Sensitivity/Response	CIViC C	EID5904
FGFR2 Y376C	AZD-4547	Sensitivity/Response	CIViC C	EID8317
FGFR2::KIAA1217 Fusion	Futibatinib	Sensitivity/Response	CIViC C	EID11611
IDH1 R132	Dasatinib	Sensitivity/Response	CIViC D	EID6439
TP53 R175H	MDM2 Inhibitor AMGMDS3	Resistance	CIViC D	EID10075