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

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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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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	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

Target	Actions	Organism
AVascular endothelial growth factor receptor 2	antagonist	Humans

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

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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
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Abciximab	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

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Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Cyramza	Solution	10 mg / mL	Intravenous	Eli Lilly & Co. Ltd.	2015-09-10	Not applicable
Cyramza	Injection, solution, concentrate	10 mg/ml	Intravenous	Eli Lilly Nederland B.V.	2020-12-20	Not applicable
Cyramza	Solution	10 mg/1mL	Intravenous	Eli Lilly and Company	2014-04-21	Not applicable
Cyramza	Injection, solution, concentrate	10 mg/ml	Intravenous	Eli Lilly Nederland B.V.	2020-12-20	Not applicable
Cyramza	Solution	10 mg/1mL	Intravenous	Eli Lilly and Company	2014-04-21	Not applicable

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
RxNav: 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

Properties

State: Solid
Experimental Properties: Not Available

Targets

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Details1. Vascular endothelial growth factor receptor 2

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

Ramucirumab

Identification

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Targets

References