Ramucirumab
Identification
- Summary
Ramucirumab is an antineoplastic agent and direct VEGFR2 (vascular endothelial growth factor receptor 2) antagonist that blocks the binding of natural VEGF ligands, which are secreted by solid tumors to promote angiogenesis and enhance tumor blood supply.
- Brand Names
- Cyramza
- Generic Name
- Ramucirumab
- DrugBank Accession Number
- DB05578
- Background
Ramucirumab is a human monoclonal antibody (IgG1) against vascular endothelial growth factor receptor 2 (VEGFR2), a type II trans-membrane tyrosine kinase receptor expressed on endothelial cells. By binding to VEGFR2, ramucirumab prevents binding of its ligands (VEGF-A, VEGF-C, and VEGF-D), thereby preventing VEGF-stimulated receptor phosphorylation and downstream ligand-induced proliferation, permeability, and migration of human endothelial cells. VEGFR stimulation also mediates downstream signalling required for angiogenesis and is postulated to be heavily involved in cancer progression, making it a highly likely drug target. In contrast to other agents directed against VEGFR-2, ramucirumab binds a specific epitope on the extracellular domain of VEGFR-2, thereby blocking all VEGF ligands from binding to it. Ramucirumab is indicated for us in advanced gastric or gastro-esophageal junction adenocarcinoma as a single agent or in combination with paclitaxel after prior fluoropyrimidine- or platinum-containing chemotherapy.
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Structure
- Protein Chemical Formula
- C6374H9864N1692O1996S46
- Protein Average Weight
- 143600.0 Da
- Sequences
>9098_H|ramucirumab|Homo sapiens||H-GAMMA-1 (VH(1-116)+CH1(117-214)+HINGE-REGION(215-229)+CH2(230-339)+CH3(340-446))|||||||446||||MW 48696.0|MW 48696.0| EVQLVQSGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSSISSSSSYIYY ADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARVTDAFDIWGQGTMVTVSSASTK GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGK
>9098_L|ramucirumab|Homo sapiens||L-KAPPA (V-KAPPA(1-107)+C-KAPPA(109-214))|||||||214||||MW 23124.7|MW 23124.7| DIQMTQSPSSVSASIGDRVTITCRASQGIDNWLGWYQQKPGKAPKLLIYDASNLDTGVPS RFSGSGSGTYFTLTISSLQAEDFAVYFCQQAKAFPPTFGGGTKVDIKGTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format- Synonyms
- Ramucirumab
- External IDs
- 1121B
- IMC-1121B
- LY3009806
Pharmacology
- Indication
Ramucirumab is indicated for the treatment of advanced or metastatic gastric or gastro-esophageal junction adenocarcinoma as a single agent or in combination with paclitaxel for patients who progress after prior fluoropyrimidine- or platinum-containing chemotherapy. It is indicated, in combination with erlotinib, for the first-line treatment of metastatic non-small cell lung cancer with epidermal growth factor exon 19 deletions or exon 21 (L858R) point mutations. It is also indicated in combination with docetaxel for the treatment of metastatic non-small cell lung cancer in patients who have progressed following prior platinum-based chemotherapy. Patients who have EGFR or ALK genomic aberrations should also have disease progression following FDA-approved therapy for these aberrations. Ramucirumab, in combination with FOLFIRI (folinic acid, fluorouracil, and irinotecan), is indicated for the treatment of metastatic colorectal cancer in patients who have progressed following therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine. Lastly, ramucirumab is indicated for the treatment of hepatocellular carcinoma in patients with an alpha-fetoprotein level ≥400 ng/mL and have previously been treated with sorafenib.9
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Advanced gastric or gastroesophageal junction (gej) adenocarcinoma Regimen in combination with: Paclitaxel (DB01229) •••••••••••• ••••• ••••••••••••••••• •• ••••••••••••••••••• ••••••••••••• •••••••••••• ••••••• ••••••••• Treatment of Advanced gastric or gastroesophageal junction (gej) adenocarcinoma •••••••••••• •••••••••••• •••••••• ••••• ••••••••••••••••• •• ••••••••••••••••••• •••••••••••• ••••••••• Treatment of Hepatocellular carcinoma •••••••••••• •••••••••• ••••••• •••• •••••••••• •••••••••••••••• •• •••• ••••• ••••••••• Used in combination to treat Metastatic colorectal cancer (crc) Regimen in combination with: Irinotecan (DB00762), Fluorouracil (DB00544), Leucovorin (DB00650) •••••••••••• •••••••• ••••••••• •••• •••••••••••• •••••••••••• ••• • ••••••••••••••••• •••••••••••• ••••••• ••••••••• Used in combination to treat Metastatic non-small cell lung cancer Regimen in combination with: Docetaxel (DB01248) •••••••••••• ••••••• ••••••••••• •• •• ••••• •••••••••••••• •••••••••••• ••••••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
Not Available
- Mechanism of action
Ramucirumab is a human monoclonal antibody (IgG1) against vascular endothelial growth factor receptor 2 (VEGFR2), a type II trans-membrane tyrosine kinase receptor expressed on endothelial cells. By binding to VEGFR2, ramucirumab prevents binding of its ligands (VEGF-A, VEGF-C, and VEGF-D), thereby preventing VEGF-stimulated receptor phosphorylation and downstream ligand-induced proliferation, permeability, and migration of human endothelial cells.
Target Actions Organism AVascular endothelial growth factor receptor 2 antagonistHumans - Absorption
Not Available
- Volume of distribution
5.5 L
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
15 days
- Clearance
0.014 L/hour
- 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
Ramucirumab packaging includes warnings for arterial thromboembolic events, hypertension, infusion-related reactions, gastrointestinal perforation, clinical deterioration in patients with cirrhosis, and reversible posterior leukoencephalopathy syndrome. The most common reactions observed in single-agent-treated patients at a rate of >10% and >2% higher than placebo were hypertension and diarrhea. The most common adverse reactions observed in patients treated with ramucirumab plus paclitaxel at a rate of of >30% and >2% higher than placebo plus paclitaxel were fatigue, neutropenia, diarrhea, and epistaxis.
- 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 Ramucirumab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Ramucirumab. Aducanumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Aducanumab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Ramucirumab. Alendronic acid The risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when Ramucirumab is combined with Alendronic acid. - 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 Cyramza Solution 10 mg / mL Intravenous Eli Lilly & Co. Ltd. 2015-09-10 Not applicable Canada Cyramza Injection, solution, concentrate 10 mg/ml Intravenous Eli Lilly Nederland B.V. 2020-12-20 Not applicable EU Cyramza Solution 10 mg/1mL Intravenous Eli Lilly and Company 2014-04-21 Not applicable US Cyramza Injection, solution, concentrate 10 mg/ml Intravenous Eli Lilly Nederland B.V. 2020-12-20 Not applicable EU Cyramza Solution 10 mg/1mL Intravenous Eli Lilly and Company 2014-04-21 Not applicable US
Categories
- ATC Codes
- L01FG02 — Ramucirumab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Antibodies
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Blood Proteins
- Cancer immunotherapy
- Globulins
- Growth Inhibitors
- Growth Substances
- Immunoglobulins
- Immunoproteins
- Immunotherapy
- MONOCLONAL ANTIBODIES AND ANTIBODY DRUG CONJUGATES
- Narrow Therapeutic Index Drugs
- Proteins
- Serum Globulins
- Vascular Endothelial Growth Factor Receptor 2 Antagonist
- VEGF/VEGFR (Vascular Endothelial Growth Factor) inhibitors
- VEGFR2 Inhibitors
- 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
- D99YVK4L0X
- CAS number
- 947687-13-0
References
- Synthesis Reference
http://www.ema.europa.eu/docs/enGB/documentlibrary/EPAR-Publicassessmentreport/human/002829/WC500180726.pdf
- General References
- Casak SJ, Fashoyin-Aje I, Lemery SJ, Zhang L, Jin R, Li H, Zhao L, Zhao H, Zhang H, Chen H, He K, Dougherty M, Novak R, Kennett S, Khasar S, Helms W, Keegan P, Pazdur R: FDA Approval Summary: Ramucirumab for Gastric Cancer. Clin Cancer Res. 2015 Aug 1;21(15):3372-6. doi: 10.1158/1078-0432.CCR-15-0600. Epub 2015 Jun 5. [Article]
- Aprile G, Rijavec E, Fontanella C, Rihawi K, Grossi F: Ramucirumab: preclinical research and clinical development. Onco Targets Ther. 2014 Oct 29;7:1997-2006. doi: 10.2147/OTT.S61132. eCollection 2014. [Article]
- Javle M, Smyth EC, Chau I: Ramucirumab: successfully targeting angiogenesis in gastric cancer. Clin Cancer Res. 2014 Dec 1;20(23):5875-81. doi: 10.1158/1078-0432.CCR-14-1071. Epub 2014 Oct 3. [Article]
- Aprile G, Bonotto M, Ongaro E, Pozzo C, Giuliani F: Critical appraisal of ramucirumab (IMC-1121B) for cancer treatment: from benchside to clinical use. Drugs. 2013 Dec;73(18):2003-15. doi: 10.1007/s40265-013-0154-8. [Article]
- Goodkin R, Zaias B, Michelsen WJ: Arteriovenous malformation and glioma: coexistent or sequential? Case report. J Neurosurg. 1990 May;72(5):798-805. [Article]
- Grothey A, Galanis E: Targeting angiogenesis: progress with anti-VEGF treatment with large molecules. Nat Rev Clin Oncol. 2009 Sep;6(9):507-18. doi: 10.1038/nrclinonc.2009.110. Epub 2009 Jul 28. [Article]
- Spratlin JL, Cohen RB, Eadens M, Gore L, Camidge DR, Diab S, Leong S, O'Bryant C, Chow LQ, Serkova NJ, Meropol NJ, Lewis NL, Chiorean EG, Fox F, Youssoufian H, Rowinsky EK, Eckhardt SG: Phase I pharmacologic and biologic study of ramucirumab (IMC-1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2. J Clin Oncol. 2010 Feb 10;28(5):780-7. doi: 10.1200/JCO.2009.23.7537. Epub 2010 Jan 4. [Article]
- Lu D, Jimenez X, Zhang H, Bohlen P, Witte L, Zhu Z: Selection of high affinity human neutralizing antibodies to VEGFR2 from a large antibody phage display library for antiangiogenesis therapy. Int J Cancer. 2002 Jan 20;97(3):393-9. [Article]
- FDA Approved Drug Products: Cyramza (ramucirumab) for intravenous injection [Link]
- External Links
- KEGG Drug
- D09371
- PubChem Substance
- 347910183
- 1535922
- ChEMBL
- CHEMBL1743062
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Ramucirumab
- FDA label
- Download (493 KB)
- MSDS
- Download (206 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 4 Recruiting Treatment Stage IV Gastric Cancer 1 3 Active Not Recruiting Treatment Colorectal Cancer 1 3 Active Not Recruiting Treatment Metastatic Non-Small Cell Lung Cancer 1 3 Completed Treatment Adenocarcinomas of the Gastroesophageal Junction / Gastric Adenocarcinoma 1 3 Completed Treatment Adenocarcinomas of the Gastroesophageal Junction / Metastatic Gastric Adenocarcinoma 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous Injection, solution, concentrate Intravenous; Parenteral 10 MG/ML Solution Intravenous 10 mg/1mL Solution Intravenous 10 mg / mL Solution Intravenous 10.000 mg Injection Parenteral 100 mg/10ml Injection, solution, concentrate Intravenous Injection Parenteral 500 mg/50ml Injection, solution, concentrate Intravenous 10 mg/ml Solution, concentrate Intravenous 10 mg Injection, solution, concentrate Intravenous 10 mg/1ml - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US2013067098 No 2011-11-02 2031-11-02 US
Properties
- State
- Solid
- 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 VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and ...
- Gene Name
- KDR
- Uniprot ID
- P35968
- Uniprot Name
- Vascular endothelial growth factor receptor 2
- Molecular Weight
- 151525.555 Da
References
- Goodkin R, Zaias B, Michelsen WJ: Arteriovenous malformation and glioma: coexistent or sequential? Case report. J Neurosurg. 1990 May;72(5):798-805. [Article]
Drug created at November 18, 2007 18:26 / Updated at July 02, 2022 12:49