Olaratumab
Identification
- Summary
Olaratumab is a platelet-derived growth factor receptor alpha blocking antibody used with doxorubicin to treat patients with certain types of soft tissue sarcoma (STS).
- Brand Names
- Lartruvo
- Generic Name
- Olaratumab
- DrugBank Accession Number
- DB06043
- Background
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
- Olaratumab
- 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.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Soft tissue sarcoma Regimen in combination with: Doxorubicin (DB00997) •••••••••••• ••••• - Contraindications & Blackbox Warnings
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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.
Target Actions Organism APlatelet-derived growth factor receptor alpha antagonistHumans - 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
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- 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.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Olaratumab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Olaratumab. Aducanumab The risk or severity of adverse effects can be increased when Olaratumab is combined with Aducanumab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Olaratumab. Alirocumab The risk or severity of adverse effects can be increased when Olaratumab is combined with Alirocumab. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Lartruvo Injection, solution, concentrate 10 mg/ml Intravenous Eli Lilly Nederland B.V. 2020-12-16 2019-09-02 EU Lartruvo Injection, solution 10 mg/1mL Intravenous Eli Lilly and Company 2016-10-19 Not applicable US Lartruvo Injection, solution, concentrate 10 mg/ml Intravenous Eli Lilly Nederland B.V. 2020-12-16 2019-09-02 EU Lartruvo Solution 190 mg / 19 mL Intravenous Eli Lilly & Co. Ltd. 2020-06-09 2020-09-25 Canada Lartruvo Injection, solution 10 mg/1mL Intravenous Eli Lilly and Company 2016-10-19 Not applicable US
Categories
- ATC Codes
- L01FX10 — Olaratumab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Blood Proteins
- Cancer immunotherapy
- Globulins
- Immunoglobulins
- Immunoproteins
- Immunotherapy
- MONOCLONAL ANTIBODIES AND ANTIBODY DRUG CONJUGATES
- Platelet-derived Growth Factor Receptor alpha Antagonist
- Proteins
- Serum Globulins
- 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
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- TT6HN20MVF
- CAS number
- 1024603-93-7
References
- General References
- 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. [Article]
- Shirley M: Olaratumab: First Global Approval. Drugs. 2016 Dec 19. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- External Links
- KEGG Drug
- D09939
- PubChem Substance
- 347910322
- 1855735
- ChEMBL
- CHEMBL1743049
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Olaratumab
- FDA label
- Download (355 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Soft Tissue Sarcoma 1 2 Completed Treatment Adult Glioblastoma 1 2 Completed Treatment Non-Small Cell Lung Cancer (NSCLC) 1 2 Completed Treatment Ovarian Neoplasms 1 2 Completed Treatment Prostate Cancer 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Intravenous 10 mg/1mL Injection, solution, concentrate Intravenous 10 mg/ml Injection, solution, concentrate Intravenous; Parenteral 10 MG/ML Solution Intravenous 190 mg / 19 mL Solution Intravenous 500 mg / 50 mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- 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
- 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. [Article]
- 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. [Article]
Drug created at November 18, 2007 18:29 / Updated at February 20, 2024 23:54