Olaratumab

Identification

Name
Olaratumab
Accession Number
DB06043
Description

Olaratumab (IMC-3G3) is a fully human IgG1 monoclonal antibody with antitumor activity that selectively binds the external domain of human platelet-derived growth factor receptor (PDGFR)-α with high affinity and blocks ligand binding. It is composed of two heavy chain molecule fragments and 2 light chain fragments. Studies show that the treatment of olaratumab in combination with doxorubicin resulted in significant reduction of cancer cell proliferation and tumor growth. Olaratumab was granted accelerated approval (as Lartruvo) as initial therapy to treat adults with certain types of soft tissue sarcoma (STS) in October, 2016.

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
C6554H10076N1736O2048S40
Protein Average Weight
154000.0 Da (147200 Da without glycan mass/154600 Da with glycan mass)
Sequences
>Heavy Chain
QLQLQESGPGLVKPSETLSLTCTVSGGSINSSSYYWGWLRQSPGKGLEWIGSFFYTGSTY
YNPSLRSRLTISVDTSKNQFSLMLSSVTAADTAVYYCARQSTYYYGSGNYYGWFDRWDQG
TLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF
PAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK
PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT
LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL
TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
>Light Chain
EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPA
RFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPAFGQGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format
Synonyms
Not Available
External IDs
  • IMC-3G3

Pharmacology

Indication

Olaratumab is indicated, in combination with doxorubicin, for the treatment of adult patients with advanced or mestastatic soft tissue sarcoma (STS) with a histologic subtype for which an anthracycline-containing regimen is appropriate and which is not amenable to curative treatment with radiotherapy or surgery.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

It exerts an anti-tumor activity in vivo and in vitro against selected sarcoma cells by inhibiting tumor growth by binding to PDGFR-alpha that is present on several types of cancer on transformed cells and in tumor stroma 3. Olaratumab antibody binding leads to inhibition of ligand-dependent signaling in PDGFR(alpha)-expressing tumor cells, as well as stromal cells in the tumor microenviroment that are dependent on PDGFR(alpha) signaling. When used in a combination therapy with doxorubicin, olaratumab improves progression-free survival in patients with advanced soft-tissue sarcoma.

Mechanism of action

Olaratumab blocks ligand-induced tumor cell proliferation, and inhibits receptor autophosphorylation and ligand-induced phosphorylation of the downstream signaling molecules protein kinase B (Akt) and mitogen-activated protein kinase 5. PDGFR signalling is a type of tyrosine kinase-mediated pathway that normally regulates cell growth, chemotaxis, and mesenchymal stem cell differentiation. It also promotes internalization of PDGFR thus alters the surface levels of PDGFR.

TargetActionsOrganism
APlatelet-derived growth factor receptor alpha
antagonist
Humans
Absorption
Not Available
Volume of distribution

7.7 L at steady state.

Protein binding

None

Metabolism

Mainly degraded nonspecifically by proteolytic enzymes

Route of elimination
Not Available
Half-life

Estimated value of 11 days

Clearance

Mean value of 0.56L/day

Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

Infusion-related reactions may occur during or after the administration which include bronchospasm, flushing, hypotension, anaphylactic shock, or cardiac arrest. Olaratumab may cause embryo-fetal toxicity based on animal data and its mechanism of action. Other reported adverse effects include neutropenia, leukopenia, anemia, nausea and musculoskeletal pain.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Olaratumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Olaratumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Olaratumab.
AlirocumabThe risk or severity of adverse effects can be increased when Olaratumab is combined with Alirocumab.
Anthrax immune globulin humanThe risk or severity of adverse effects can be increased when Olaratumab is combined with Anthrax immune globulin human.
Antilymphocyte immunoglobulin (horse)The risk or severity of adverse effects can be increased when Olaratumab is combined with Antilymphocyte immunoglobulin (horse).
Antithymocyte immunoglobulin (rabbit)The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Olaratumab.
Asfotase alfaThe risk or severity of adverse effects can be increased when Olaratumab is combined with Asfotase alfa.
AtezolizumabThe risk or severity of adverse effects can be increased when Olaratumab is combined with Atezolizumab.
AvelumabThe risk or severity of adverse effects can be increased when Olaratumab is combined with Avelumab.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

Products

Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
LartruvoInjection, solution10 mg/1mLIntravenousEli Lilly and Company2016-10-19Not applicableUs
LartruvoSolution190 mgIntravenousEli Lilly & Co. Ltd.2020-06-09Not applicableCanada
LartruvoInjection, solution10 mg/1mLIntravenousEli Lilly and Company2016-10-19Not applicableUs
LartruvoSolution500 mgIntravenousEli Lilly & Co. Ltd.2017-12-222020-06-19Canada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
L01XC27 — Olaratumab
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Chemical Identifiers

UNII
TT6HN20MVF
CAS number
1024603-93-7

References

General References
  1. Dolloff NG, Russell MR, Loizos N, Fatatis A: Human bone marrow activates the Akt pathway in metastatic prostate cells through transactivation of the alpha-platelet-derived growth factor receptor. Cancer Res. 2007 Jan 15;67(2):555-62. [PubMed:17234763]
  2. Shirley M: Olaratumab: First Global Approval. Drugs. 2016 Dec 19. [PubMed:27995580]
  3. Doi T, Ma Y, Dontabhaktuni A, Nippgen C, Nippgen J, Ohtsu A: Phase I study of olaratumab in Japanese patients with advanced solid tumors. Cancer Sci. 2014 Jul;105(7):862-9. doi: 10.1111/cas.12444. Epub 2014 Jun 27. [PubMed:24816152]
  4. Knepper TC, Saller J, Walko CM: Novel and Expanded Oncology Drug Approvals of 2016-PART 1: New Options in Solid Tumor Management. Oncology (Williston Park). 2017 Feb 15;31(2):110-21. [PubMed:28205191]
  5. Wagner AJ, Kindler H, Gelderblom H, Schoffski P, Bauer S, Hohenberger P, Kopp HG, Lopez-Martin JA, Peeters M, Reichardt P, Qin A, Nippgen J, Ilaria RL, Rutkowski P: A phase II study of a human anti-PDGFRalpha monoclonal antibody (olaratumab, IMC-3G3) in previously treated patients with metastatic gastrointestinal stromal tumors. Ann Oncol. 2017 Mar 1;28(3):541-546. doi: 10.1093/annonc/mdw659. [PubMed:28426120]
  6. Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, Agulnik M, Cooney MM, Livingston MB, Pennock G, Hameed MR, Shah GD, Qin A, Shahir A, Cronier DM, Ilaria R Jr, Conti I, Cosaert J, Schwartz GK: Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016 Jul 30;388(10043):488-97. doi: 10.1016/S0140-6736(16)30587-6. Epub 2016 Jun 9. [PubMed:27291997]
KEGG Drug
D09939
PubChem Substance
347910322
RxNav
1855735
ChEMBL
CHEMBL1743049
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Olaratumab
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (355 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentSoft Tissue Sarcoma (STS)1
2CompletedTreatmentAdult Glioblastoma Multiforme / Brain and Central Nervous System Tumors1
2CompletedTreatmentGastrointestinal Stromal Tumors (GISTs)1
2CompletedTreatmentNeoplasms, Ovarian1
2CompletedTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
2CompletedTreatmentProstate Cancer1
2TerminatedTreatmentAdvanced Soft Tissue Sarcoma1
1Active Not RecruitingTreatmentSoft Tissue Sarcoma (STS)1
1CompletedNot AvailableTumors, Solid1
1CompletedBasic ScienceSoft Tissue Sarcoma (STS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solutionIntravenous10 mg/1mL
SolutionIntravenous190 mg
SolutionIntravenous500 mg
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chem...
Gene Name
PDGFRA
Uniprot ID
P16234
Uniprot Name
Platelet-derived growth factor receptor alpha
Molecular Weight
122668.46 Da
References
  1. van der Graaf WT: Olaratumab in soft-tissue sarcomas. Lancet. 2016 Jul 30;388(10043):442-4. doi: 10.1016/S0140-6736(16)30788-7. Epub 2016 Jun 9. [PubMed:27291995]
  2. Doi T, Ma Y, Dontabhaktuni A, Nippgen C, Nippgen J, Ohtsu A: Phase I study of olaratumab in Japanese patients with advanced solid tumors. Cancer Sci. 2014 Jul;105(7):862-9. doi: 10.1111/cas.12444. Epub 2014 Jun 27. [PubMed:24816152]

Drug created on November 18, 2007 11:29 / Updated on August 14, 2020 04:24

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