Teprotumumab

Summary

Teprotumumab (CHEMBL1743079) is an approved antibody (ATC L04AG13) targeting IGF1R; indicated across 6 conditions including sarcoma and non-small cell lung carcinoma; with CIViC clinical evidence for 3 variant-indication associations (e.g. KRAS Mutation in lung non-small cell carcinoma).

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Antibody
• ATC class: L04AG13
• Targets: 1 (IGF1R)
• Indications: 6 conditions
• Clinical trials: 25
• Precision-oncology evidence (CIViC): 3 variant–indication associations

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1743079
Name	Teprotumumab
Type	Antibody
Max phase	4
ATC	L04AG13

Also known as: HZN-001, HZN001, Onilcamotide, R-1507, RG-1507, RG1507, Rhoc peptide vaccine rv001v, RO-4858696, RO-4858696000, RO4858696, RV-001, RV-001 MONOCLONAL

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
IGF1R	Insulin-like growth factor I receptor	Antagonist	12.16	19%	P08069

Bioactivity

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

Target pathways

Aggregated over 1 target gene(s): IGF1R.

Top Reactome pathways

5 total, by targets touching each:

Pathway	Targets	Genes
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)	1	IGF1R
IRS-related events triggered by IGF1R	1	IGF1R
SHC-related events triggered by IGF1R	1	IGF1R
Extra-nuclear estrogen signaling	1	IGF1R
Respiratory syncytial virus (RSV) attachment and entry	1	IGF1R

Dominant GO biological processes

GO term	Targets
immune response	1
signal transduction	1
positive regulation of cell population proliferation	1
insulin receptor signaling pathway	1
positive regulation of cell migration	1
peptidyl-tyrosine autophosphorylation	1
negative regulation of apoptotic process	1
positive regulation of protein-containing complex disassembly	1
negative regulation of MAPK cascade	1
positive regulation of MAPK cascade	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
transcytosis	1
regulation of JNK cascade	1
protein autophosphorylation	1
insulin-like growth factor receptor signaling pathway	1

Indications & clinical

Indications

6 indications (1 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
sarcoma	2	MONDO:0005089	EFO:0000691
non-small cell lung carcinoma	2	MONDO:0005233	EFO:0003060
breast neoplasm	2	MONDO:0021100	MONDO:0007254
neoplasm	1	MONDO:0005070	EFO:0000616
diffuse scleroderma	1	MONDO:0005019	EFO:0000404

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

Clinical trials

Total trials: 25.

Phase distribution

Phase	Trials
PHASE1	11
PHASE2	6
PHASE4	3
PHASE3	3
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07265258	PHASE4	NOT_YET_RECRUITING	A Study of Teprotumumab N01 in Subjects With Active Thyroid Eye Disease
NCT04583735	PHASE4	COMPLETED	A Study Evaluating TEPEZZA® Treatment in Patients With Chronic (Inactive) Thyroid Eye Disease
NCT05002998	PHASE4	COMPLETED	TEPEZZA® (Teprotumumab-trbw) Post-Marketing Requirement Study
NCT06248619	PHASE3	ACTIVE_NOT_RECRUITING	A Trial to Investigate Teprotumumab Subcutaneous Administration Compared With Placebo in Male and Female Adult Participants With Moderate-to-severe Active Thyroid Eye Disease
NCT03298867	PHASE3	COMPLETED	Treatment of Graves’ Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis With Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study
NCT03461211	PHASE3	COMPLETED	Treatment of Graves’ Orbitopathy to Reduce Proptosis With Teprotumumab Infusions in an Open-Label Clinical Extension Study
NCT07594912	PHASE2	NOT_YET_RECRUITING	Teprotumumab N01 Versus Methylprednisolone After Urgent Orbital Decompression for Dysthyroid Optic Neuropathy
NCT00642941	PHASE2	TERMINATED	A Study of R1507 in Participants With Recurrent or Refractory Sarcoma
NCT00760929	PHASE2	TERMINATED	A Study of the Effect of R1507 in Combination With Tarceva (Erlotinib) on Progression-Free Survival in Patients With Stage IIIb/IV Non-Small Cell Lung Cancer (NSCLC).
NCT00773383	PHASE2	TERMINATED	A Study of the Effect of R1507 in Combination With Tarceva (Erlotinib) on Progression-Free Survival in Patients With Stage IIIb/IV Non-Small Cell Lung Cancer (NSCLC) Having Received Tarceva Monotherapy.
NCT00796107	PHASE2	TERMINATED	A Study of R1507 in Combination With Letrozole in Postmenopausal Women With Advanced Breast Cancer
NCT01868997	PHASE2	COMPLETED	Teprotumumab (RV 001) Treatment in Patients With Active Thyroid Eye Disease
NCT00400361	PHASE1	COMPLETED	A Multiple Ascending Dose Study of R1507 in Patients With Advanced Solid Tumors.
NCT00560144	PHASE1	COMPLETED	A Multiple Ascending Dose Study of R1507 in Children and Adolescents With Advanced Solid Tumors.
NCT00811993	PHASE1	TERMINATED	A Study of R1507 in Combination With Multiple Standard Chemotherapy Treatments in Patients With Advanced Solid Tumors
NCT00882674	PHASE1	COMPLETED	A Study to Evaluate the Biological Activity of R1507 in Women With Operable Breast Cancer
NCT00985374	PHASE1	TERMINATED	A Multiple Ascending Dose Study of the mTOR Inhibitor (RAD001) in Combination With R1507 in Patients With Advanced Solid Tumors
NCT02103283	PHASE1	COMPLETED	A Phase 1, Open-Label Study of Teprotumumab in Patients With Diabetic Macular Edema (DME)
NCT04478994	PHASE1	TERMINATED	A Study With TEPEZZA in Patients With Diffuse Cutaneous Systemic Sclerosis (dcSSc)
NCT06389578	PHASE1	COMPLETED	A Study of TEPEZZA® Treatment in Participants With Thyroid Eye Disease
NCT06563856	PHASE1	COMPLETED	A Study of TEPEZZA Subcutaneous Administration in Healthy Adults
NCT06674941	PHASE1	COMPLETED	A Trial to Investigate Teprotumumab (High-concentration Formulation) Subcutaneous Administration in Healthy Adult Non-Japanese and Japanese Participants
NCT07142642	PHASE1	COMPLETED	A Study to Evaluate Pharmacokinetics, Safety, and Tolerability of Teprotumumab (AMG 632) Administered Intravenously in Healthy Chinese Participants
NCT04040894	Not specified	APPROVED_FOR_MARKETING	Expanded Access Protocol of Teprotumumab (HZN-001) for Patients With Active Thyroid Eye Disease
NCT07085117	Not specified	COMPLETED	Real World Study to Describe the Effectiveness and Safety of Teprotumumab Among Thyroid Eye Disease Patients

Clinical evidence (CIViC)

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

Variant	Indication	Effect	Therapy	Level	CIViC
KRAS Mutation	Lung Non-small Cell Carcinoma	Sensitivity/Response	Teprotumumab + Erlotinib	CIViC B	EID3713
PTPRD V253I	Ewing Sarcoma Of Bone	Sensitivity/Response	Cixutumumab + Teprotumumab	CIViC C	EID1856
KRAS Mutation	Colorectal Cancer	Sensitivity/Response	Teprotumumab + Selumetinib	CIViC D	EID1004

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.

28 molecules share ≥1 primary target. Top 28 by shared-target count:

Molecule	Source	Status	Shared targets
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	IGF1R
PAZOPANIB	ChEMBL + PubChem	Phase 4 (approved)	IGF1R
BRIGATINIB	ChEMBL	Phase 4 (approved)	IGF1R
CERITINIB	ChEMBL	Phase 4 (approved)	IGF1R
ENTRECTINIB	ChEMBL	Phase 4 (approved)	IGF1R
FEDRATINIB	ChEMBL	Phase 4 (approved)	IGF1R
NINTEDANIB	ChEMBL	Phase 4 (approved)	IGF1R
SUNITINIB	ChEMBL	Phase 4 (approved)	IGF1R
LESTAURTINIB	ChEMBL	Phase 3	IGF1R
LINSITINIB	ChEMBL	Phase 3	IGF1R
QUERCETIN	ChEMBL	Phase 3	IGF1R
BMS-754807	ChEMBL	Phase 2	IGF1R
CENISERTIB	ChEMBL	Phase 2	IGF1R
ELLAGIC ACID	ChEMBL	Phase 2	IGF1R
FORETINIB	ChEMBL	Phase 2	IGF1R
ILORASERTIB	ChEMBL	Phase 2	IGF1R
R-406	ChEMBL	Phase 2	IGF1R
TOZASERTIB	ChEMBL	Phase 2	IGF1R
Afatinib	PubChem	Approved	IGF1R
belumosudil	PubChem	Approved	IGF1R
Binimetinib	PubChem	Approved	IGF1R
dacomitinib	PubChem	Approved	IGF1R
Fostamatinib	PubChem	Approved	IGF1R
Gefitinib	PubChem	Approved	IGF1R
Idelalisib	PubChem	Approved	IGF1R
regorafenib	PubChem	Approved	IGF1R
Selumetinib	PubChem	Approved	IGF1R
Trametinib	PubChem	Approved	IGF1R