Zenocutuzumab

Summary

Zenocutuzumab (CHEMBL4298025) is an approved antibody targeting ERBB3; indicated across 4 conditions including non-small cell lung carcinoma and pancreatic neoplasm; with CIViC clinical evidence for 2 variant-indication associations (e.g. NRG1 Fusion in lung non-small cell carcinoma).

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Antibody
• Targets: 1 (ERBB3)
• Indications: 4 conditions
• Clinical trials: 4
• Precision-oncology evidence (CIViC): 2 variant–indication associations

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4298025
Name	Zenocutuzumab
Type	Antibody
Max phase	4

Also known as: Bizengri, Mcla 128, Mcla-128, MCLA-128, MCLA128, Zenocutuzumab, Zenocutuzumab-zbco, ZENOCUTUZUMAB

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
ERBB3	erb-b2 receptor tyrosine kinase 3	Antagonist	10.46	7.9%	P21860

Bioactivity

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

Target pathways

Aggregated over 1 target gene(s): ERBB3.

Top Reactome pathways

15 total, by targets touching each:

Pathway	Targets	Genes
Signaling by ERBB2	1	ERBB3
Signaling by ERBB4	1	ERBB3
SHC1 events in ERBB2 signaling	1	ERBB3
PIP3 activates AKT signaling	1	ERBB3
GRB7 events in ERBB2 signaling	1	ERBB3
Downregulation of ERBB2:ERBB3 signaling	1	ERBB3
PI3K events in ERBB2 signaling	1	ERBB3
Constitutive Signaling by Aberrant PI3K in Cancer	1	ERBB3
RAF/MAP kinase cascade	1	ERBB3
ERBB2 Regulates Cell Motility	1	ERBB3
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	ERBB3
ERBB2 Activates PTK6 Signaling	1	ERBB3
Downregulation of ERBB2 signaling	1	ERBB3
Signaling by ERBB2 KD Mutants	1	ERBB3
Signaling by ERBB2 TMD/JMD mutants	1	ERBB3

Dominant GO biological processes

GO term	Targets
endocardial cushion development	1
negative regulation of cell adhesion	1
signal transduction	1
cell surface receptor protein tyrosine kinase signaling pathway	1
epidermal growth factor receptor signaling pathway	1
peripheral nervous system development	1
heart development	1
negative regulation of signal transduction	1
positive regulation of gene expression	1
Schwann cell differentiation	1
Schwann cell development	1
cranial nerve development	1
neuron differentiation	1
ERBB2-ERBB3 signaling pathway	1
wound healing	1

Indications & clinical

Indications

4 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
non-small cell lung carcinoma	4	MONDO:0005233	MONDO:0005233
pancreatic neoplasm	4	MONDO:0021040	MONDO:0021040
breast neoplasm	2	MONDO:0021100	MONDO:0007254
neoplasm	1	MONDO:0005070	EFO:0000616

Clinical trials

Total trials: 4.

Phase distribution

Phase	Trials
PHASE2	3
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02912949	PHASE2	ACTIVE_NOT_RECRUITING	A Study of Zenocutuzumab (MCLA-128) in Patients With Solid Tumors Harboring an NRG1 Fusion (eNRGy)
NCT03321981	PHASE2	COMPLETED	MCLA-128 With Trastuzumab/Chemotherapy in HER2+ and With Endocrine Therapy in ER+ and Low HER2 Breast Cancer.
NCT05588609	PHASE2	TERMINATED	Study Evaluating Zenocutuzumab in Patients With or Without Molecularly Defined Cancers
NCT04100694	Not specified	APPROVED_FOR_MARKETING	Early Access Program Providing HER2/HER3 Bispecific Antibody, MCLA-128, for a Patient With Advanced NRG1-Fusion Positive Solid Tumor

Clinical evidence (CIViC)

Variant × indication × effect (2 predictive associations from 2 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
NRG1 Fusion	Lung Non-small Cell Carcinoma	Sensitivity/Response	Zenocutuzumab-zbco	CIViC A	EID12246
NRG1 Fusion	Pancreatic Adenocarcinoma	Sensitivity/Response	Zenocutuzumab-zbco	CIViC A	EID12247

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.

37 molecules share ≥1 primary target. Top 37 by shared-target count:

Molecule	Source	Status	Shared targets
AFATINIB	ChEMBL + PubChem	Phase 4 (approved)	ERBB3
BOSUTINIB	ChEMBL + PubChem	Phase 4 (approved)	ERBB3
ERLOTINIB	ChEMBL + PubChem	Phase 4 (approved)	ERBB3
GEFITINIB	ChEMBL + PubChem	Phase 4 (approved)	ERBB3
LAPATINIB	ChEMBL + PubChem	Phase 4 (approved)	ERBB3
MOBOCERTINIB	ChEMBL + PubChem	Phase 4 (approved)	ERBB3
NERATINIB	ChEMBL + PubChem	Phase 4 (approved)	ERBB3
OSIMERTINIB	ChEMBL + PubChem	Phase 4 (approved)	ERBB3
VANDETANIB	ChEMBL + PubChem	Phase 4 (approved)	ERBB3
DASATINIB	ChEMBL	Phase 4 (approved)	ERBB3
ALVOCIDIB	ChEMBL	Phase 3	ERBB3
CANERTINIB	ChEMBL	Phase 3	ERBB3
CEDIRANIB	ChEMBL	Phase 3	ERBB3
LESTAURTINIB	ChEMBL	Phase 3	ERBB3
ROCILETINIB	ChEMBL	Phase 3	ERBB3
AEE-788	ChEMBL	Phase 2	ERBB3
FORETINIB	ChEMBL	Phase 2	ERBB3
MAVELERTINIB	ChEMBL	Phase 2	ERBB3
PF-06459988	ChEMBL	Phase 2	ERBB3
SAPITINIB	ChEMBL	Phase 2	ERBB3
TOZASERTIB	ChEMBL	Phase 2	ERBB3
Acalabrutinib	PubChem	Approved	ERBB3
Axitinib	PubChem	Approved	ERBB3
Crizotinib	PubChem	Approved	ERBB3
dacomitinib	PubChem	Approved	ERBB3
Fedratinib	PubChem	Approved	ERBB3
Ibrutinib	PubChem	Approved	ERBB3
Imatinib	PubChem	Approved	ERBB3
Midostaurin	PubChem	Approved	ERBB3
Nilotinib	PubChem	Approved	ERBB3
Pazopanib	PubChem	Approved	ERBB3
Quizartinib	PubChem	Approved	ERBB3
Ruxolitinib	PubChem	Approved	ERBB3
Selumetinib	PubChem	Approved	ERBB3
Sorafenib	PubChem	Approved	ERBB3
Sunitinib	PubChem	Approved	ERBB3
Tofacitinib	PubChem	Approved	ERBB3