Savolitinib

Summary

Savolitinib (CHEMBL3334567) is a phase-3 clinical-stage small-molecule c-Met tyrosine kinase inhibitor targeting MET; indicated across 14 conditions including renal cell carcinoma and non-small cell lung carcinoma; with CIViC clinical evidence for 3 variant-indication associations (e.g. MET Amplification in stomach cancer).

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (MET)
• Indications: 14 conditions
• Clinical trials: 42
• Precision-oncology evidence (CIViC): 3 variant–indication associations
• Chemistry: 345.4 Da · C17H15N9

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3334567
Name	Savolitinib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	68289010
ChEBI	CHEBI:231369
Molecular formula	C17H15N9
Molecular weight	345.4
InChIKey	XYDNMOZJKOGZLS-NSHDSACASA-N

SMILES: C[C@@H](C1=CN2C=CN=C2C=C1)N3C4=NC(=CN=C4N=N3)C5=CN(N=C5)C

IUPAC name: 3-[(1S)-1-imidazo[1,2-a]pyridin-6-ylethyl]-5-(1-methylpyrazol-4-yl)triazolo[4,5-b]pyrazine

ChEBI definition: A member of the class of triazolopyrazines that is 1H-[1,2,3]triazolo[4,5-b]pyrazine substituted by (1S)-1-(imidazo[1,2-a]pyridin-6-yl)ethyl and 1-methyl-1H-pyrazol-4-yl groups at positions 1 and 6, respectively. It is a highly selective MET tyrosine kinase inhibitor that is approved in China for advanced NSCLC with MET exon 14 skipping mutations.

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

Also known as: Azd-6094, AZD-6094, AZD6094, HMPL-504, Savolitinib, Volitinib, SAVOLITINIB

Patent coverage: 513 distinct patent families (1,199 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 1,194 (100%) 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	8.3	2.4%	P08581

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Hepatocyte growth factor receptor, Ribosyldihydronicotinamide dehydrogenase [quinone].

Bioactivity

ChEMBL activities: 7 potent at pChembl ≥ 5 of 7 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
MET	8.85	IC50	1.42	nM	CHEMBL_ACT_29234293
MET	8.7	IC50	2	nM	CHEMBL_ACT_19100626
MET	8.52	IC50	3	nM	CHEMBL_ACT_15075689
MET	8.32	IC50	4.77	nM	CHEMBL_ACT_25922423
MET	8.3	IC50	5	nM	CHEMBL_ACT_15075664
NQO2	6.69	Kd	206	nM	CHEMBL_ACT_17922257
MET	6.17	IC50	676.1	nM	CHEMBL_ACT_19100646

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

14 indications (0 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
renal cell carcinoma	3	MONDO:0005086	EFO:0000681
non-small cell lung carcinoma	3	MONDO:0005233	EFO:0003060
papillary renal cell carcinoma	3	MONDO:0017884	EFO:0000640
gastric adenocarcinoma	2	MONDO:0005036	EFO:0000503
carcinoma	2	MONDO:0004993	EFO:0000313
rectal cancer	2	MONDO:0006519	EFO:1000657
colon adenocarcinoma	2	MONDO:0002271	EFO:1001949
gastric neoplasm	2	MONDO:0021085	MONDO:0001056
lung neoplasm	2	MONDO:0021117	MONDO:0008903
neoplasm	1	MONDO:0005070	EFO:0000616
colorectal neoplasm	1	MONDO:0005335	MONDO:0005575

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

Clinical trials

Total trials: 42.

Phase distribution

Phase	Trials
PHASE2	20
PHASE1	14
PHASE3	6
PHASE1/PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03091192	PHASE3	ACTIVE_NOT_RECRUITING	Savolitinib vs. Sunitinib in MET-driven PRCC.
NCT05009836	PHASE3	ACTIVE_NOT_RECRUITING	Clinical Study on Savolitinib + Osimertinib in Treatment of EGFRm+/MET+ Locally Advanced or Metastatic NSCLC
NCT05043090	PHASE3	ACTIVE_NOT_RECRUITING	Savolitinib Plus Durvalumab Versus Sunitinib and Durvalumab Monotherapy in MET-Driven, Unresectable and Locally Advanced or Metastatic PRCC
NCT05261399	PHASE3	ACTIVE_NOT_RECRUITING	Savolitinib Plus Osimertinib Versus Platinum-based Doublet Chemotherapy in Participants With Non-Small Cell Lung Cancer Who Have Progressed on Osimertinib Treatment
NCT04923945	PHASE3	COMPLETED	Savolitinib for Treating Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) Patients
NCT05015608	PHASE3	COMPLETED	Study on Savolitinib Combined With Osimertinib in Treatment of Advanced NSCLC With MET Amplification
NCT03385655	PHASE2	ACTIVE_NOT_RECRUITING	Prostate Cancer Biomarker Enrichment and Treatment Selection
NCT03778229	PHASE2	ACTIVE_NOT_RECRUITING	Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib
NCT03833440	PHASE2	ACTIVE_NOT_RECRUITING	Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance
NCT03944772	PHASE2	ACTIVE_NOT_RECRUITING	Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Who Progressed on First-Line Osimertinib Therapy (ORCHARD)
NCT04322890	PHASE2	RECRUITING	Treatment Strategies and Survival Outcome for Non-small Cell Lung Cancer With Oncogenic Mutation
NCT04606771	PHASE2	ACTIVE_NOT_RECRUITING	A Study Comparing Savolitinib Plus Osimertinib vs Savolitinib Plus Placebo in Patients With EGFRm+ and MET Amplified Advanced NSCLC
NCT05163249	PHASE2	ACTIVE_NOT_RECRUITING	Osimertinib With or Without Savolitinib as 1L in de Novo MET+, EGFR+ NSCLC
NCT05374603	PHASE2	ACTIVE_NOT_RECRUITING	Savolitinib Combine With Durvalumab in EGFR Wild-type Locally Advanced or Metastatic NSCLC
NCT05620628	PHASE2	RECRUITING	Ph2 Study of Savolitinib and Durvalumab (MEDI4736) Combination in Advanced MET Amplified Gastric Cancer(VIKTORY-2)
NCT05777278	PHASE1/PHASE2	RECRUITING	Savolitinib Plus Docetaxel as 2L in EGFR/ALK/ROS1/MET ex14m-wildtype NSCLC With MET Overexpression
NCT06563999	PHASE2	RECRUITING	Neoadjuvant Umbrella Trial for Patients With Unresectable Stage III NSCLC Harboring Rare Mutations.
NCT06692491	PHASE2	NOT_YET_RECRUITING	Study of Precision Treatment for Rare Tumours in China Guided by PDO and NGS
NCT02117167	PHASE2	COMPLETED	SAFIR02_Lung - Efficacy of Targeted Drugs Guided by Genomic Profiles in Metastatic NSCLC Patients
NCT02127710	PHASE2	COMPLETED	A Phase II Trial to Evaluate the Efficacy of AZD6094 (HMPL-504) in Patients With Papillary Renal Cell Carcinoma (PRCC)
NCT02447380	PHASE2	COMPLETED	Study of AZD6094 (Volitinib) in Combination With Docetaxel, in Advanced Gastric Adenocarcinoma Patients With MET Overexpression as a Second-line Treatment
NCT02447406	PHASE1/PHASE2	COMPLETED	Phase Ib, Single-arm Study of AZD6094 (Volitinib) in Combination With Docetaxel, in Any Solid Cancer and Sequential Phase II, Single-arm Study of AZD6094 (Volitinib) in Combination With Docetaxel in Advanced Gastric Adenocarcinoma Patients With MET Amplification as a Second Line Treatment
NCT02449551	PHASE2	COMPLETED	Study of AZD6094 (Volitinib) in Advanced Gastric Adenocarcinoma Patients With MET Amplification as a Third-line Treatment
NCT02761057	PHASE2	COMPLETED	Testing Cabozantinib, Crizotinib, Savolitinib and Sunitinib in Kidney Cancer Which Has Progressed
NCT02819596	PHASE2	COMPLETED	MEDI4736 Combinations in Metastatic Renal Cell Carcinoma
NCT02897479	PHASE2	UNKNOWN	A Phase II Study of HMPL-504 in Lung Sarcomatoid Carcinoma and Other Non-small Cell Lung Cancer
NCT03592641	PHASE2	TERMINATED	Savolitinib in Treating Patients With MET Amplified Metastatic or Unresectable Colorectal Cancer
NCT04923932	PHASE2	COMPLETED	Savolitinib for Treating Gastric Cancer and Esophagogastric Junction Adenocarcinoma Patients
NCT03598244	PHASE1	ACTIVE_NOT_RECRUITING	Volitinib in Treating Patients With Recurrent or Refractory Primary CNS Tumors
NCT01773018	PHASE1	COMPLETED	Phase I Study of the Volitinib (HMPL-504) in Patients With Advanced Solid Tumors
NCT02017236	PHASE1	COMPLETED	A Food Effect Phase I Study of the Volitinib in Healthy Subjects
NCT02252913	PHASE1	COMPLETED	A Study of Safety and Pharmacokinetics of Volitinib With Docetaxel in Patients With Advanced Gastric Cancer
NCT02374645	PHASE1	COMPLETED	A Phase I Study of Safety and Pharmacokinetics of Volitinib in Combination With Gefitinib in EGFR(+) NSCLC
NCT02630420	PHASE1	WITHDRAWN	Cetuximab and Savolitinib Treatment of Ras Wild-Type Colorectal Cancer
NCT03258515	PHASE1	COMPLETED	A Study to Investigate the Effect of Single Dose of AZD6094 (600 mg) on Cardiac Repolarization in Healthy Volunteers
NCT04118842	PHASE1	COMPLETED	A Study in Healthy Subjects to Assess the Pharmacokinetics of Savolitinib When Administered Alone and in Combination With Rifampicin
NCT04121910	PHASE1	COMPLETED	A Study to Evaluate the Amount of Drug That Becomes Available in the Blood Circulation When Savolitinib is Administered Alone and in Combination With Itraconazole
NCT04179071	PHASE1	COMPLETED	A Study in Healthy Male Subjects to Understand How Savolitinib Behaves Inside the Body (Pharmacokinetics) When Administered Alone and in Combination With Famotidine
NCT04187456	PHASE1	COMPLETED	A Study in Healthy Male Subjects to Understand How Savolitinib When Taken With Midazolam Behaves Inside the Body
NCT05768360	PHASE1	COMPLETED	A Study to Assess the Effects of Savolitinib on the Pharmacokinetics of Digoxin, Rosuvastatin, Metformin, and Furosemide in Healthy Male Subjects

Clinical evidence (CIViC)

Variant × indication × effect (3 predictive associations from 3 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
MET Amplification	Stomach Cancer	Sensitivity/Response	Savolitinib	CIViC B	EID7729
MET Exon 14 Skipping Mutation	Lung Adenocarcinoma	Sensitivity/Response	Savolitinib	CIViC C	EID11474
MET D1228V	Lung Non-small Cell Carcinoma	Resistance	Savolitinib	CIViC C	EID1865

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
CAPMATINIB	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
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