Lazertinib

Summary

Lazertinib (CHEMBL4558324) is an approved small molecule (ATC L01EB09) targeting EGFR, KDR, and JAK3; indicated across 6 conditions including non-small cell lung carcinoma and neoplasm; with CIViC clinical evidence for 3 variant-indication associations (e.g. EGFR L858R OR EGFR Exon 19 Deletion in lung non-small cell carcinoma).

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L01EB09
• Targets: 4 (EGFR, KDR, JAK3…)
• Indications: 6 conditions
• Clinical trials: 39
• Precision-oncology evidence (CIViC): 3 variant–indication associations
• Chemistry: 554.6 Da · C30H34N8O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4558324
Name	Lazertinib
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	121269225
ATC	L01EB09
Molecular formula	C30H34N8O3
Molecular weight	554.6
InChIKey	RRMJMHOQSALEJJ-UHFFFAOYSA-N

SMILES: CN(C)CC1=CN(N=C1C2=CC=CC=C2)C3=NC(=NC=C3)NC4=C(C=C(C(=C4)NC(=O)C=C)N5CCOCC5)OC

IUPAC name: N-[5-[[4-[4-[(dimethylamino)methyl]-3-phenylpyrazol-1-yl]pyrimidin-2-yl]amino]-4-methoxy-2-morpholin-4-ylphenyl]prop-2-enamide

Also known as: GNS-1480, GNS1480, Lazertinib, YH-25448, Yh25448, YH25448, LAZERTINIB

Parent form; salt/anhydrous children: CHEMBL6068478

Patent coverage: 511 distinct patent families (1,311 SureChEMBL compound mentions), from 1 matched compound structure(s). 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
EGFR	epidermal growth factor receptor	Inhibition	7.7	17.5%	P00533
KDR	kinase insert domain receptor	Inhibition	6	1.1%	P35968
JAK3	Janus kinase 3	Inhibition	7.7	0.6%	P52333
SYK	spleen associated tyrosine kinase	Inhibition	6.7	2%	P43405

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Receptor tyrosine-protein kinase erbB-2, Epidermal 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
EGFR	8.57	IC50	2.7	nM	CHEMBL_ACT_22782722
EGFR	8.33	Ki	4.68	nM	CHEMBL_ACT_25942050
EGFR	7.47	Ki	34	nM	CHEMBL_ACT_24750262
EGFR	7.47	Ki	34	nM	CHEMBL_ACT_25942059
EGFR	7.46	IC50	34.6	nM	CHEMBL_ACT_22782712
EGFR	6.57	Ki	271	nM	CHEMBL_ACT_24750253
EGFR	6.57	Ki	271	nM	CHEMBL_ACT_25942033
ERBB2	6.36	Ki	437	nM	CHEMBL_ACT_24750271

Target pathways

Aggregated over 4 target gene(s): EGFR, KDR, JAK3, SYK.

Top Reactome pathways

102 total, by targets touching each:

Pathway	Targets	Genes
Cytokine Signaling in Immune system	2	JAK3, SYK
Signal Transduction	2	JAK3, SYK
Disease	2	JAK3, SYK
Immune System	2	JAK3, SYK
Signaling by Interleukins	2	JAK3, SYK
Interleukin-2 family signaling	2	JAK3, SYK
Interleukin-3, Interleukin-5 and GM-CSF signaling	2	JAK3, SYK
Infectious disease	2	JAK3, SYK
RAF/MAP kinase cascade	2	EGFR, JAK3
Interleukin-2 signaling	2	JAK3, SYK
Potential therapeutics for SARS	2	JAK3, SYK
SARS-CoV Infections	2	JAK3, SYK
Viral Infection Pathways	2	JAK3, SYK
Hemostasis	1	SYK
GPVI-mediated activation cascade	1	SYK
Signaling by ERBB2	1	EGFR
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	1	EGFR
Signaling by ERBB4	1	EGFR
SHC1 events in ERBB2 signaling	1	EGFR
PLCG1 events in ERBB2 signaling	1	EGFR
PIP3 activates AKT signaling	1	EGFR
Interleukin-7 signaling	1	JAK3
Adaptive Immune System	1	SYK
Innate Immune System	1	SYK
Signaling by EGFR	1	EGFR
GRB2 events in EGFR signaling	1	EGFR
GAB1 signalosome	1	EGFR
SHC1 events in EGFR signaling	1	EGFR
EGFR downregulation	1	EGFR
Neuropilin interactions with VEGF and VEGFR	1	KDR

Dominant GO biological processes

GO term	Targets
protein phosphorylation	4
positive regulation of MAPK cascade	3
positive regulation of protein phosphorylation	2
cell surface receptor signaling pathway	2
positive regulation of cell population proliferation	2
positive regulation of cell migration	2
negative regulation of apoptotic process	2
epithelial cell proliferation	2
positive regulation of epithelial cell proliferation	2
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	2
positive regulation of ERK1 and ERK2 cascade	2
cell surface receptor protein tyrosine kinase signaling pathway	2
angiogenesis	2
lymph vessel development	2
peptidyl-tyrosine phosphorylation	2

Indications & clinical

Indications

6 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
non-small cell lung carcinoma	3	MONDO:0005233	EFO:0003060
neoplasm	3	MONDO:0005070	EFO:0000616
lung neoplasm	2	MONDO:0021117	MONDO:0021117
liver disorder	1	MONDO:0005154	EFO:0001421

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

Clinical trials

Total trials: 39.

Phase distribution

Phase	Trials
PHASE2	21
PHASE1	8
PHASE3	4
Not specified	4
PHASE1/PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04487080	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer
NCT04988295	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non- Small Cell Lung Cancer After Osimertinib Failure
NCT05388669	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Lazertinib With Subcutaneous Amivantamab Compared With Intravenous Amivantamab in Participants With Epidermal Growth Factor Receptor (EGFR)-Mutated Advanced or Metastatic Non-small Cell Lung Cancer
NCT04248829	PHASE3	COMPLETED	Clinical Trial of YH25448(Lazertinib) as the First-line Treatment in Patients With EGFR Mutation Positive Locally Advanced or Metastatic NSCLC (LASER301)
NCT05299125	PHASE2	ACTIVE_NOT_RECRUITING	Amivantamab, Lazertinib, and Pemetrexed for First-line Treatment of Recurrent/Metastatic Non-small Cell Lung Cancers With Epidermal Growth Factor Receptor Mutations
NCT05463224	PHASE2	ACTIVE_NOT_RECRUITING	Lazertinib for NSCLC Harboring Activating EGFR Mutations in TKI naïve Patients
NCT05469022	PHASE2	RECRUITING	Neoadjuvant Lazertinib Therapy in EGFR-Mutation Positive Lung Adenocarcinoma Detected by BALF Liquid Biopsy
NCT05498428	PHASE2	RECRUITING	A Study of Amivantamab in Participants With Advanced or Metastatic Solid Tumors Including Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer
NCT05541822	PHASE2	RECRUITING	To Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetic Profile of ABN401 in Patients With Advanced Solid Tumors Harboring c-MET Dysregulation
NCT05601973	PHASE2	ACTIVE_NOT_RECRUITING	Amivantamab, Lazertinib and Bevacizumab in Patients With EGFR-mutant Advanced Non-small Cell Lung Cancer With Progression on Previous Third-generation EGFR-TKI
NCT05663866	PHASE2	ACTIVE_NOT_RECRUITING	Premedication to Reduce Amivantamab Associated Infusion Related Reactions
NCT05786430	PHASE2	ACTIVE_NOT_RECRUITING	Lazertinib+Pemetrexed/Carboplatin in Patients With EGFR Sensitizing Mutation Positive Recurrent or Metastatic Non-Small Cell Lung Cancer Failed to Prior Lazertinib
NCT06106802	PHASE2	RECRUITING	Lazertinib & Tepotinib for EGFR Mutant NSCLC in MET Overexpressed or Amplified Who Progressed After Lazertinib Treatment
NCT06120140	PHASE2	ACTIVE_NOT_RECRUITING	Enhanced Dermatological Care to Reduce Rash and Paronychia in Epidermal Growth Factor Receptor (EGRF)-Mutated Non-Small Cell Lung Cancer (NSCLC) Treated First-line With Amivantamab Plus Lazertinib
NCT06156527	PHASE2	RECRUITING	A Randomized Phase II Study of LAZE rtiNib Alone Versus Lazertinib Plus bevaCizumab for NSCLC With EGFR + & Smoker
NCT06268210	PHASE2	RECRUITING	Neoadjuvant Lazertinib With or Without Chemotherapy for Patients With EGFR-mutated Resectable Non-small Cell Lung Cancer
NCT06667076	PHASE2	RECRUITING	A Study of Amivantamab in Combination With Lazertinib, or Amivantamab in Combination With Platinum-Based Chemotherapy, for Common Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)
NCT07586202	PHASE2	NOT_YET_RECRUITING	A Study of Neoadjuvant Amivantamab With Either Lazertinib or Chemotherapy in Participants With Resectable EGFR-Mutated NSCLC
NCT03046992	PHASE1/PHASE2	COMPLETED	Clinical Trial of YH25448 in Patients with EGFR Mutation Positive Advanced NSCLC
NCT04075396	PHASE1/PHASE2	COMPLETED	A Study of Lazertinib in Participants With Epidermal Growth Factor Receptor (EGFR) Mutation Positive Advanced Non-Small Cell Lung Cancer (NSCLC)
NCT04965090	PHASE2	COMPLETED	A Study of Amivantamab and Lazertinib in People With Non-Small Cell Lung Cancer (NSCLC)
NCT05167851	PHASE2	UNKNOWN	The Safety and Efficacy of First-line Lazertinib and Locally Ablative Radiotherapy in Patients With Synchronous Oligo-metastatic EGFR-mutant Non-small Cell Lung Cancer
NCT05277701	PHASE2	UNKNOWN	Lazertinib for Patients With NSCLC Harboring Uncommon EGFR Mutations
NCT05338619	PHASE2	UNKNOWN	A Study of Lazertinib as Consolidation Therapy in Patients With Locally Advanced, Unresectable, EGFR-Mutant Non-Small Cell Lung Cancer (Stage III) Following Chemoradiation Therapy
NCT05477615	PHASE2	UNKNOWN	Lazertinib/Pemetrexed/Carboplatin After Osimertinib Failure in NSCLC With Brain Metastases
NCT05701384	PHASE2	UNKNOWN	Lazertinib 160mg in EGFR T790M NSCLC
NCT06020989	PHASE2	UNKNOWN	Lazertinib and Chemotherapy Combination in EGFR-mutant NSCLC Patients Without ctDNA Clearance After lead-in Lazertinib Monotherapy
NCT02609776	PHASE1	ACTIVE_NOT_RECRUITING	Study of Amivantamab, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer
NCT04077463	PHASE1	ACTIVE_NOT_RECRUITING	A Study of Lazertinib as Monotherapy or in Combination With Amivantamab in Participants With Advanced Non-small Cell Lung Cancer
NCT03556436	PHASE1	COMPLETED	Clinical Trial to Evaluate the Safety and Effects of Ethnicity and Food on Pharmacokinetics of YH25448
NCT04410094	PHASE1	COMPLETED	A Study to Assess the Effects of Itraconazole and Rifampin on Lazertinib in Healthy Adult Participants
NCT05076877	PHASE1	COMPLETED	A Study of Lazertinib (JNJ-73841937) in Healthy Participants
NCT05112952	PHASE1	COMPLETED	A Study to Evaluate the Effect of Hepatic Impairment on Lazertinib (JNJ-73841937)
NCT05742594	PHASE1	COMPLETED	A Study of Four Different Oral Tablet Formulations of Lazertinib (JNJ-73841937) in Healthy Adult Participants
NCT05896683	PHASE1	COMPLETED	A Study of Lazertinib (JNJ-73841937) Tablet in Healthy Adult Participants
NCT04829422	Not specified	APPROVED_FOR_MARKETING	Early Access Program of Lazertinib in Republic of Korea
NCT05377788	Not specified	UNKNOWN	Lazertinib Real-world Observational Study of in Pre-treated EGFR T790M Mutant With Advanced Non-small Cell Lung Cancer
NCT05716672	Not specified	UNKNOWN	Impact of Lazertinib Dose Modification on Effectiveness and Safety
NCT05862194	Not specified	COMPLETED	Retrospective, External Comparator Study of Lazertinib as the 2nd-Line Treatment in Patients With EGFR Mutation+ NSCLC

Clinical evidence (CIViC)

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

Variant	Indication	Effect	Therapy	Level	CIViC
EGFR L858R OR EGFR Exon 19 Deletion	Lung Non-small Cell Carcinoma	Sensitivity/Response	Lazertinib + Amivantamab	CIViC A	EID12131
EGFR Mutation	Lung Non-small Cell Carcinoma	Sensitivity/Response	Amivantamab + Lazertinib	CIViC B	EID12928
EGFR T790M	Lung Non-small Cell Carcinoma	Sensitivity/Response	Lazertinib	CIViC D	EID12783

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 1 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

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

Molecule	Source	Status	Shared targets
AFATINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, JAK3, KDR, SYK
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, JAK3, KDR, SYK
GEFITINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, JAK3, KDR, SYK
Pazopanib	ChEMBL + PubChem	Phase 4 (approved)	EGFR, JAK3, KDR, SYK
SELUMETINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, JAK3, KDR, SYK
CERITINIB	ChEMBL	Phase 4 (approved)	EGFR, JAK3, KDR, SYK
DASATINIB	ChEMBL	Phase 4 (approved)	EGFR, JAK3, KDR, SYK
ERLOTINIB	ChEMBL	Phase 4 (approved)	EGFR, JAK3, KDR, SYK
FEDRATINIB	ChEMBL	Phase 4 (approved)	EGFR, JAK3, KDR, SYK
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	EGFR, JAK3, KDR, SYK
NERATINIB	ChEMBL	Phase 4 (approved)	EGFR, JAK3, KDR, SYK
LESTAURTINIB	ChEMBL	Phase 3	EGFR, JAK3, KDR, SYK
CENISERTIB	ChEMBL	Phase 2	EGFR, JAK3, KDR, SYK
PELITINIB	ChEMBL	Phase 2	EGFR, JAK3, KDR, SYK
R-406	ChEMBL	Phase 2	EGFR, JAK3, KDR, SYK
TOZASERTIB	ChEMBL	Phase 2	EGFR, JAK3, KDR, SYK
DACOMITINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, JAK3, SYK
ACALABRUTINIB	ChEMBL	Phase 4 (approved)	EGFR, JAK3, KDR
AXITINIB	ChEMBL	Phase 4 (approved)	EGFR, JAK3, KDR
BOSUTINIB	ChEMBL	Phase 4 (approved)	EGFR, JAK3, SYK
ENTRECTINIB	ChEMBL	Phase 4 (approved)	JAK3, KDR, SYK
IBRUTINIB	ChEMBL	Phase 4 (approved)	EGFR, JAK3, KDR
IMATINIB	ChEMBL	Phase 4 (approved)	EGFR, KDR, SYK
OSIMERTINIB	ChEMBL	Phase 4 (approved)	EGFR, JAK3, KDR
SORAFENIB	ChEMBL	Phase 4 (approved)	EGFR, JAK3, KDR
SUNITINIB	ChEMBL	Phase 4 (approved)	EGFR, JAK3, KDR
CANERTINIB	ChEMBL	Phase 3	EGFR, JAK3, KDR
CEDIRANIB	ChEMBL	Phase 3	EGFR, KDR, SYK
DOVITINIB	ChEMBL	Phase 3	EGFR, JAK3, KDR
QUERCETIN	ChEMBL	Phase 3	EGFR, KDR, SYK
AT-9283	ChEMBL	Phase 2	JAK3, KDR, SYK
FORETINIB	ChEMBL	Phase 2	EGFR, KDR, SYK
ILORASERTIB	ChEMBL	Phase 2	EGFR, KDR, SYK
MIVAVOTINIB	ChEMBL	Phase 2	JAK3, KDR, SYK
SOTRASTAURIN	ChEMBL	Phase 2	EGFR, JAK3, KDR
SU-014813	ChEMBL	Phase 2	EGFR, JAK3, KDR
Binimetinib	PubChem	Approved	EGFR, KDR, SYK
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	EGFR, KDR
MOBOCERTINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, JAK3
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	KDR, SYK
ABEMACICLIB	ChEMBL	Phase 4 (approved)	EGFR, KDR
ABROCITINIB	ChEMBL	Phase 4 (approved)	JAK3, KDR
ALECTINIB	ChEMBL	Phase 4 (approved)	EGFR, KDR
BRIGATINIB	ChEMBL	Phase 4 (approved)	EGFR, KDR
CABOZANTINIB	ChEMBL	Phase 4 (approved)	EGFR, KDR
FOSTAMATINIB DISODIUM	ChEMBL	Phase 4 (approved)	KDR, SYK
GILTERITINIB	ChEMBL	Phase 4 (approved)	EGFR, SYK
HEXACHLOROPHENE	ChEMBL	Phase 4 (approved)	EGFR, KDR
INFIGRATINIB	ChEMBL	Phase 4 (approved)	KDR, SYK
NICLOSAMIDE	ChEMBL	Phase 4 (approved)	EGFR, KDR
NINTEDANIB	ChEMBL	Phase 4 (approved)	JAK3, KDR
OLMUTINIB	ChEMBL	Phase 4 (approved)	EGFR, KDR
PONATINIB	ChEMBL	Phase 4 (approved)	EGFR, KDR
TOFACITINIB	ChEMBL	Phase 4 (approved)	JAK3, KDR
UPADACITINIB	ChEMBL	Phase 4 (approved)	JAK3, KDR
VANDETANIB	ChEMBL	Phase 4 (approved)	EGFR, KDR
VEMURAFENIB	ChEMBL	Phase 4 (approved)	EGFR, KDR
ZANUBRUTINIB	ChEMBL	Phase 4 (approved)	EGFR, JAK3
ABIVERTINIB	ChEMBL	Phase 3	EGFR, JAK3
ALISERTIB	ChEMBL	Phase 3	EGFR, KDR