Onartuzumab

Summary

Onartuzumab (CHEMBL1743051) is a phase-3 clinical-stage antibody targeting MET; indicated across 9 conditions including neoplasm and non-small cell lung carcinoma; with CIViC clinical evidence for 1 variant-indication association (e.g. MET Amplification in gastric adenocarcinoma).

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Antibody
• Targets: 1 (MET)
• Indications: 9 conditions
• Clinical trials: 16
• Precision-oncology evidence (CIViC): 1 variant–indication association

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1743051
Name	Onartuzumab
Type	Antibody
Max phase	3

Also known as: METMA-B, Metmab, Onartuzumab, PRO-143966, PRO-143996, PRO143966, RO-5490258, RO5490258, ONARTUZUMAB

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	Binding	8.37	2.4%	P08581

Bioactivity

No ChEMBL bioactivity rows at pChembl ≥ 5 (expected for biologics / antibodies).

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

9 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
neoplasm	3	MONDO:0005070	EFO:0000616
non-small cell lung carcinoma	3	MONDO:0005233	EFO:0003060
gastric neoplasm	3	MONDO:0021085	MONDO:0001056
glioblastoma	2	MONDO:0018177	EFO:0000519
breast neoplasm	2	MONDO:0021100	MONDO:0007254
colorectal neoplasm	2	MONDO:0005335	MONDO:0005575
hepatocellular carcinoma	1	MONDO:0007256	EFO:0000182
lung neoplasm	1	MONDO:0021117	MONDO:0008903

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

Clinical trials

Total trials: 16.

Phase distribution

Phase	Trials
PHASE2	7
PHASE3	5
PHASE1	3
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01456325	PHASE3	COMPLETED	A Study of Onartuzumab (MetMAb) in Combination With Tarceva (Erlotinib) in Participants With Met Diagnostic-Positive Non-Small Cell Lung Cancer Who Have Received Chemotherapy For Advanced or Metastatic Disease (MetLung)
NCT01662869	PHASE3	COMPLETED	A Study of Onartuzumab in Combination With mFOLFOX6 in Participants With Metastatic HER2-Negative and MET-Positive Gastroesophageal Cancer
NCT01887886	PHASE3	COMPLETED	A Study of Onartuzumab in Combination With Erlotinib in Patients With MET-Positive Stage IIIB or IV Non-Small Cell Lung Cancer Carrying an Activating Epidermal Growth Factor Receptor (EGFR) Mutation
NCT02031744	PHASE3	COMPLETED	A Study of the Efficacy and Safety of MetMAb Combined With Tarceva in Patients With Met-Positive Non-Small Cell Lung Cancer
NCT02488330	PHASE3	COMPLETED	An Extension Study of Onartuzumab in Participants With Solid Tumors on Study Treatment Previously Enrolled in a Company Sponsored Study
NCT00854308	PHASE2	COMPLETED	A Study of MetMAb Administered to Patients With Advanced Non-Small Cell Lung Cancer, in Combination With Tarceva (Erlotinib)
NCT01186991	PHASE2	COMPLETED	Study Evaluating the Safety and Efficacy of Onartuzumab And/or Bevacizumab in Combination With Paclitaxel in Participants With Metastatic, Triple Negative Breast Cancer
NCT01418222	PHASE2	COMPLETED	FOLFOX/Bevacizumab With Onartuzumab (MetMAb) Versus Placebo as First-Line Treatment in Patients With Metastatic Colorectal Cancer
NCT01496742	PHASE2	COMPLETED	A Study of Onartuzumab (MetMAb) in Combination With Bevacizumab (Avastin) Plus Platinum And Paclitaxel or With Pemetrexed Plus Platinum in Patients With Non-Squamous Non-Small Cell Lung Cancer
NCT01519804	PHASE2	COMPLETED	A Study of Onartuzumab (MetMAb) Versus Placebo in Combination With Paclitaxel Plus Platinum in Patients With Squamous Non-Small Cell Lung Cancer
NCT01590719	PHASE2	COMPLETED	A Study of Onartuzumab (MetMAb) in Combination With mFOLFOX6 in Patients With Metastatic Human Epidermal Growth Factor Receptor 2 (HER2) Negative Gastroesophageal Cancer
NCT01632228	PHASE2	COMPLETED	A Study of Onartuzumab (MetMAb) in Combination With Bevacizumab Compared to Bevacizumab Alone or Onartuzumab Monotherapy in Participants With Recurrent Glioblastoma
NCT02044601	PHASE1/PHASE2	WITHDRAWN	Biomarker-Integrated Approach of Targeted Therapy for Lung Cancer Elimination Plus External Beam Radiation Therapy (BATTLE-XRT)
NCT01068977	PHASE1	COMPLETED	A Study of the Safety and Pharmacology of MetMAb (PRO143966), a Monovalent Antagonist Antibody to the Receptor C-Met, Administered Intravenously in Patients With Locally Advanced or Metastatic Solid Tumors
NCT01897038	PHASE1	COMPLETED	A Safety, Tolerability, and Pharmacokinetics Study of Onartuzumab as Single Agent or in Combination With Sorafenib in Participants With Advanced Hepatocellular Carcinoma
NCT01974258	PHASE1	WITHDRAWN	Safety, Tolerability, and Pharmacokinetics of Onartuzumab Combined With Vemurafenib and/or Cobimetinib in Cancer Patients

Clinical evidence (CIViC)

Variant × indication × effect (1 predictive associations from 1 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
MET Amplification	Gastric Adenocarcinoma	Sensitivity/Response	Onartuzumab	CIViC C	EID689

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

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.

84 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
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