Capmatinib

Summary

Capmatinib (CHEMBL3188267) is an approved small-molecule c-Met tyrosine kinase inhibitor (ATC L01EX17) targeting MET; indicated across 12 conditions including neoplasm and non-small cell lung carcinoma; with CIViC clinical evidence for 15 variant-indication associations (e.g. MET Exon 14 Skipping Mutation in lung non-small cell carcinoma).

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L01EX17
• Targets: 1 (MET)
• Indications: 12 conditions
• Clinical trials: 52
• Precision-oncology evidence (CIViC): 15 variant–indication associations
• Chemistry: 412.4 Da · C23H17FN6O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3188267
Name	Capmatinib
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	25145656
ChEBI	CHEBI:231693
ATC	L01EX17
Molecular formula	C23H17FN6O
Molecular weight	412.4
InChIKey	LIOLIMKSCNQPLV-UHFFFAOYSA-N

SMILES: CNC(=O)C1=C(C=C(C=C1)C2=NN3C(=CN=C3N=C2)CC4=CC5=C(C=C4)N=CC=C5)F

IUPAC name: 2-fluoro-N-methyl-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide

ChEBI definition: A member of the class of imidazotriazines that is imidazo[1,2-b][1,2,4]triazine substituted by 3-fluoro-4-(methylcarbamoyl)phenyl and quinolin-6-ylmethyl groups at positions 2 and 7, respectively. It is a c-Met receptor tyrosine kinase inhibitor used for the treatment of non-small cell lung cancer with MET exon 14 skipping mutation.

Pharmacological roles (ChEBI): c-Met tyrosine kinase inhibitor, antineoplastic agent, hepatotoxic agent, apoptosis inducer.

Also known as: Capmatinib, INC-280, INC280, Incb-28060, INCB-28060, INCB-28060 FREE BASE, NVP-INC280, CAPMATINIB, INCB28060, INCB-28060A-1419, INCB 28060, CAPMATINIB (INCB28060)

Parent form; salt/anhydrous children: CHEMBL3989937

Patent coverage: 1,155 distinct patent families (2,884 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 2,508 (87%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
MET	MET proto-oncogene, receptor tyrosine kinase	Inhibition	9.89	2.4%	P08581

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Cyclin-dependent kinase-like 5, Hepatocyte growth factor receptor.

Bioactivity

ChEMBL activities: 8 potent at pChembl ≥ 5 of 8 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
MET	9.89	IC50	0.13	nM	CHEMBL_ACT_16466224
MET	9.89	IC50	0.13	nM	CHEMBL_ACT_25527160
MET	9.89	IC50	0.13	nM	CHEMBL_ACT_25595646
MET	9.89	IC50	0.13	nM	CHEMBL_ACT_29055495
MET	9.52	Kd	0.3	nM	CHEMBL_ACT_17919070
MET	9.4	IC50	0.4	nM	CHEMBL_ACT_18096042
MET	9.15	IC50	0.7	nM	CHEMBL_ACT_29320098
CDKL5	5.69	Kd	2042	nM	CHEMBL_ACT_17891530

Target pathways

Aggregated over 1 target gene(s): MET.

Top Reactome pathways

44 total, by targets touching each:

Pathway	Targets	Genes
PIP3 activates AKT signaling	1	MET
Developmental Biology	1	MET
Signal Transduction	1	MET
Disease	1	MET
Negative regulation of the PI3K/AKT network	1	MET
Generic Transcription Pathway	1	MET
PI3K/AKT Signaling in Cancer	1	MET
Constitutive Signaling by Aberrant PI3K in Cancer	1	MET
Semaphorin interactions	1	MET
Sema4D in semaphorin signaling	1	MET
Sema4D mediated inhibition of cell attachment and migration	1	MET
Axon guidance	1	MET
Diseases of signal transduction by growth factor receptors and second messengers	1	MET
Infectious disease	1	MET
RAF/MAP kinase cascade	1	MET
MAPK family signaling cascades	1	MET
MAPK1/MAPK3 signaling	1	MET
Signaling by MET	1	MET
MET Receptor Activation	1	MET
Negative regulation of MET activity	1	MET
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	MET
RNA Polymerase II Transcription	1	MET
Gene expression (Transcription)	1	MET
MET activates RAS signaling	1	MET
MET activates PI3K/AKT signaling	1	MET
MET activates PTPN11	1	MET
MET activates PTK2 signaling	1	MET
InlB-mediated entry of Listeria monocytogenes into host cell	1	MET
MET interacts with TNS proteins	1	MET
MET activates RAP1 and RAC1	1	MET

Dominant GO biological processes

GO term	Targets
endothelial cell morphogenesis	1
liver development	1
cell surface receptor signaling pathway	1
cell surface receptor protein tyrosine kinase signaling pathway	1
negative regulation of autophagy	1
neuron differentiation	1
pancreas development	1
positive regulation of transcription by RNA polymerase II	1
hepatocyte growth factor receptor signaling pathway	1
branching morphogenesis of an epithelial tube	1
positive chemotaxis	1
excitatory postsynaptic potential	1
semaphorin-plexin signaling pathway	1
negative regulation of hydrogen peroxide-mediated programmed cell death	1
positive regulation of endothelial cell chemotaxis	1

Indications & clinical

Indications

12 indications (2 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
neoplasm	4	MONDO:0005070	EFO:0000616
non-small cell lung carcinoma	3	MONDO:0005233	EFO:0003060
soft tissue sarcoma	3	MONDO:0018078	EFO:1001968
hepatocellular carcinoma	2	MONDO:0007256	EFO:0000182
cutaneous melanoma	2	MONDO:0005012	EFO:0000389
melanoma	2	MONDO:0005105	EFO:0000756
kidney cancer	2	MONDO:0002367	MONDO:0002367
lung neoplasm	2	MONDO:0021117	MONDO:0008903
glioblastoma	1	MONDO:0018177	EFO:0000519
liver disorder	1	MONDO:0005154	EFO:0001421
breast neoplasm	1	MONDO:0021100	MONDO:0007254

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 52.

Phase distribution

Phase	Trials
PHASE2	24
PHASE1	12
PHASE1/PHASE2	6
Not specified	4
PHASE3	3
PHASE2/PHASE3	2
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05110196	PHASE4	COMPLETED	Study of Capmatinib in Indian Patients With MET Exon 14 Skipping Mutation Positive Advanced NSCLC.
NCT05722886	PHASE2/PHASE3	RECRUITING	DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial) - Master Screening Protocol
NCT06988475	PHASE2/PHASE3	RECRUITING	DETERMINE Trial Treatment Arm 06: Capmatinib in Adult Patients With Cancers Harbouring MET Dysregulations
NCT03784014	PHASE3	COMPLETED	Molecular Profiling of Advanced Soft-tissue Sarcomas
NCT04427072	PHASE3	TERMINATED	Study of Capmatinib Efficacy in Comparison With Docetaxel in Previously Treated Participants With Non-small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutation
NCT04816214	PHASE3	TERMINATED	Study Evaluating Efficacy and Safety of Capmatinib in Combination With Osimertinib in Adult Subjects With Non-small Cell Lung Cancers as Second Line Therapy
NCT02813135	PHASE1/PHASE2	RECRUITING	European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumors
NCT03040973	PHASE2	ACTIVE_NOT_RECRUITING	Study to Allow Patients Previously Participating in a Novartis Sponsored Trial to Continue Receiving Capmatinib Treatment as Single Agent or in Combination With Other Treatments or the Combination Treatment Alone
NCT05488314	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study of Amivantamab and Capmatinib Combination Therapy in Unresectable Metastatic Non-small Cell Lung Cancer
NCT05642572	PHASE2	RECRUITING	Comparing Combinations of Targeted Drugs for Advanced Non-Small Cell Lung Cancer That Has EGFR and MET Gene Changes (A Lung-MAP Treatment Trial)
NCT06054191	PHASE2	NOT_YET_RECRUITING	Neoadjuvant and Adjuvant Targeted Treatment in NSCLC With BRAF V600 or MET Exon 14 Mutations
NCT01610336	PHASE2	COMPLETED	A Safety and Efficacy Study of INC280 and Gefitinib in Patients With EGFR Mutated, c-MET-amplified NSCLC Who Have Progressed After EGFRi Treatment
NCT01737827	PHASE2	TERMINATED	Study Efficacy and Safety of INC280 in Patients With Advanced Hepatocellular Carcinoma.
NCT01870726	PHASE1/PHASE2	TERMINATED	Safety and Efficacy of INC280 and Buparlisib (BKM120) in Patients With Recurrent Glioblastoma
NCT01964235	PHASE2	WITHDRAWN	Study of Efficacy and Safety INC280 in Patients With Advanced Hepatocellular Carcinoma
NCT02019693	PHASE2	COMPLETED	A Phase 2 Study of the MET Kinase Inhibitor INC280 in Papillary Renal Cell Cancer
NCT02159066	PHASE2	COMPLETED	LGX818 and MEK162 in Combination With a Third Agent (BKM120, LEE011, BGJ398 or INC280) in Advanced BRAF Melanoma
NCT02276027	PHASE2	COMPLETED	A Phase II, Open Label, Multiple Arm Study of AUY922, BYL719, INC280, LDK378 and MEK162 in Chinese Patients With Advanced Non-small Cell Lung Cancer
NCT02323126	PHASE2	TERMINATED	Study of Efficacy and Safety of Nivolumab in Combination With EGF816 and of Nivolumab in Combination With INC280 in Patients With Previously Treated Non-small Cell Lung Cancer
NCT02335944	PHASE1/PHASE2	TERMINATED	Study of Safety and Efficacy of EGFR-TKI EGF816 in Combination With cMET Inhibitor INC280 in Adult Patients With EGFR Mutated Non Small Cell Lung Cancer.
NCT02414139	PHASE2	COMPLETED	Study of Oral cMET Inhibitor INC280 in Patients With EGFR Wild-type (wt), Advanced Non-small Cell Lung Cancer (NSCLC) (Geometry Mono-1)
NCT02587650	PHASE2	TERMINATED	Capmatinib, Ceritinib, Regorafenib, or Entrectinib in Treating Patients With BRAF/NRAS Wild-Type Stage III-IV Melanoma
NCT02750215	PHASE2	COMPLETED	A Study of Capmatinib (INC280) in NSCLC Patients With MET Exon 14 Alterations Who Have Received Prior MET Inhibitor
NCT02795429	PHASE1/PHASE2	COMPLETED	Phase Ib/II Study of INC280 + PDR001 or PDR001 Single Agent in Advanced HCC
NCT03240393	PHASE2	WITHDRAWN	Study of Oral cMET Inhibitor INC280 in Chinese Patients With EGFR Wild-type Advanced Non-small Cell Lung Cancer (NSCLC)
NCT03484923	PHASE2	COMPLETED	Study of Efficacy and Safety of Novel Spartalizumab Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma
NCT03647488	PHASE2	COMPLETED	Study of Capmatinib and Spartalizumab Combination Therapy vs Docetaxel in Non-small Cell Lung Cancer
NCT03693339	PHASE2	UNKNOWN	Capmatinib in Patients With Non-small Cell Lung Cancer Harboring cMET exon14 Skipping Mutation
NCT04139317	PHASE2	TERMINATED	Safety and Efficacy of Capmatinib (INC280) Plus Pembrolizumab vs Pembrolizumab Alone in NSCLC With PD-L1≥ 50%
NCT04323436	PHASE2	TERMINATED	Study of Capmatinib and Spartalizumab/Placebo in Advanced NSCLC Patients With MET Exon 14 Skipping Mutations
NCT04460729	PHASE2	WITHDRAWN	A Phase II, Open-Label, Multicenter Study of Capmatinib in Subjects With MET Exon 14 Skipping Mutation Positive, Advanced, NSCLC With Brain Metastases
NCT04677595	PHASE2	COMPLETED	Study of Capmatinib in Chinese Adult Patients With Advanced Non-small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutation
NCT04926831	PHASE2	TERMINATED	Phase II of Neoadjuvant and Adjuvant Capmatinib in NSCLC
NCT05135845	PHASE2	SUSPENDED	Combination of Capmatinib + Spartalizumab in Advanced Oesogastric Adenocarcinoma
NCT05243641	PHASE1/PHASE2	TERMINATED	Neratinib and Capmatinib Combination (Phase Ib/II) in Metastatic Breast Cancer and Inflammatory Breast Cancer Patients With Abnormal HER-family and c-Met Pathway Activity as Measured by the CELsignia Signaling Analysis Test
NCT05567055	PHASE2	WITHDRAWN	Central Nervous System Efficacy of Capmatinib in NSCLC With Brain Metastases With cfDNA Positive MET Alterations
NCT03333343	PHASE1	ACTIVE_NOT_RECRUITING	Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC
NCT01324479	PHASE1	COMPLETED	Study of INC280 in Patients With c-MET Dependent Advanced Solid Tumors
NCT01546428	PHASE1	COMPLETED	A Phase I Study of INC280 in Japanese Patients With Advanced Solid Tumors
NCT01911507	PHASE1	COMPLETED	INC280 and Erlotinib Hydrochloride in Treating Patients With Non-small Cell Lung Cancer

Clinical evidence (CIViC)

Variant × indication × effect (15 predictive associations from 18 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
MET Exon 14 Skipping Mutation	Lung Non-small Cell Carcinoma	Sensitivity/Response	Capmatinib	CIViC A	EID8847 +2
MET Amplification	Lung Non-small Cell Carcinoma	Sensitivity/Response	Capmatinib	CIViC B	EID8849
MET Amplification OR MET Exon 14 Skipping Mutation	Lung Non-small Cell Carcinoma	Sensitivity/Response	Capmatinib	CIViC B	EID11458
MET Exon 14 Skipping Mutation	Lung Adenocarcinoma	Sensitivity/Response	Capmatinib	CIViC C	EID11417 +1
EGFR Exon 19 Deletion AND MET Y1003N	Lung Adenocarcinoma	Sensitivity/Response	Osimertinib + Capmatinib	CIViC C	EID11418
EGFR L858R AND MET Amplification	Lung Non-small Cell Carcinoma	Sensitivity/Response	Gefitinib + Capmatinib	CIViC C	EID11408
EGFR T790M AND EGFR Exon 19 Deletion AND MET Splice Site (c.3027_3028+21delAGGTATATTTCAGTTTATTGTTC	Lung Adenocarcinoma	Sensitivity/Response	Capmatinib + Osimertinib	CIViC C	EID11693
KIF5B::MET e24::e15	Lung Adenocarcinoma	Sensitivity/Response	Capmatinib	CIViC C	EID12384
MET Splice Site (c.3028+2T>C)	Lung Adenocarcinoma	Sensitivity/Response	Capmatinib + Tepotinib	CIViC C	EID11412
MET Amplification AND MYC Amplification	Lung Adenocarcinoma	Resistance	Capmatinib	CIViC C	EID11420
MET Exon 14 Skipping Mutation	Lung Non-small Cell Carcinoma	Adverse Response	Capmatinib	CIViC C	EID11409
MET Exon 14 Skipping Mutation	Lung Cancer	Adverse Response	Capmatinib	CIViC C	EID11459
BRAF D594N AND BRAF G466A	Collecting Duct Carcinoma	Sensitivity/Response	Capmatinib + Crizotinib	CIViC D	EID12449
MET Amplification AND MYC Amplification	Lung Adenocarcinoma	Sensitivity/Response	Capmatinib + ICX-101	CIViC D	EID11421
MET Exon 14 Skipping Mutation	Cancer	Sensitivity/Response	Capmatinib	CIViC D	EID7797

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

83 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
AFATINIB	ChEMBL + PubChem	Phase 4 (approved)	MET
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	MET
PAZOPANIB	ChEMBL + PubChem	Phase 4 (approved)	MET
AFATINIB DIMALEATE	ChEMBL	Phase 4 (approved)	MET
AXITINIB	ChEMBL	Phase 4 (approved)	MET
BOSUTINIB	ChEMBL	Phase 4 (approved)	MET
BRIGATINIB	ChEMBL	Phase 4 (approved)	MET
CABOZANTINIB	ChEMBL	Phase 4 (approved)	MET
CABOZANTINIB S-MALATE	ChEMBL	Phase 4 (approved)	MET
CERITINIB	ChEMBL	Phase 4 (approved)	MET
DABRAFENIB	ChEMBL	Phase 4 (approved)	MET
ENSARTINIB	ChEMBL	Phase 4 (approved)	MET
ENTRECTINIB	ChEMBL	Phase 4 (approved)	MET
ERLOTINIB	ChEMBL	Phase 4 (approved)	MET
FEDRATINIB	ChEMBL	Phase 4 (approved)	MET
GEFITINIB	ChEMBL	Phase 4 (approved)	MET
INFIGRATINIB	ChEMBL	Phase 4 (approved)	MET
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	MET
NERATINIB	ChEMBL	Phase 4 (approved)	MET
NINTEDANIB	ChEMBL	Phase 4 (approved)	MET
PALBOCICLIB	ChEMBL	Phase 4 (approved)	MET
SORAFENIB	ChEMBL	Phase 4 (approved)	MET
SUNITINIB	ChEMBL	Phase 4 (approved)	MET
TEPOTINIB	ChEMBL	Phase 4 (approved)	MET
TIVOZANIB	ChEMBL	Phase 4 (approved)	MET
VANDETANIB	ChEMBL	Phase 4 (approved)	MET
CANERTINIB	ChEMBL	Phase 3	MET
CEDIRANIB	ChEMBL	Phase 3	MET
DACTOLISIB	ChEMBL	Phase 3	MET
ENZASTAURIN	ChEMBL	Phase 3	MET
EPIGALOCATECHIN GALLATE	ChEMBL	Phase 3	MET
LESTAURTINIB	ChEMBL	Phase 3	MET
LINIFANIB	ChEMBL	Phase 3	MET
LINSITINIB	ChEMBL	Phase 3	MET
POZIOTINIB	ChEMBL	Phase 3	MET
QUERCETIN	ChEMBL	Phase 3	MET
RIGOSERTIB	ChEMBL	Phase 3	MET
SAVOLITINIB	ChEMBL	Phase 3	MET
SITRAVATINIB	ChEMBL	Phase 3	MET
TIVANTINIB	ChEMBL	Phase 3	MET
ALTIRATINIB	ChEMBL	Phase 2	MET
AMG-208	ChEMBL	Phase 2	MET
AMG-337	ChEMBL	Phase 2	MET
AT-9283	ChEMBL	Phase 2	MET
BEMCENTINIB	ChEMBL	Phase 2	MET
BI-2536	ChEMBL	Phase 2	MET
BMS-754807	ChEMBL	Phase 2	MET
BMS-777607	ChEMBL	Phase 2	MET
CENISERTIB	ChEMBL	Phase 2	MET
CEP-32496	ChEMBL	Phase 2	MET
DALMELITINIB	ChEMBL	Phase 2	MET
DECERNOTINIB	ChEMBL	Phase 2	MET
DEFOSBARASERTIB	ChEMBL	Phase 2	MET
ELLAGIC ACID	ChEMBL	Phase 2	MET
ELZOVANTINIB	ChEMBL	Phase 2	MET
ENVONALKIB	ChEMBL	Phase 2	MET
FORETINIB	ChEMBL	Phase 2	MET
GLESATINIB	ChEMBL	Phase 2	MET
GOLVATINIB	ChEMBL	Phase 2	MET
GUMARONTINIB	ChEMBL	Phase 2	MET