Identification

Name
Ramucirumab
Accession Number
DB05578
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Description

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.

Protein structure
Db05578
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
Not Available
External IDs
1121B / IMC-1121B / LY3009806
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CyramzaSolution10 mgIntravenousEli Lilly & Co. Ltd.2015-09-10Not applicableCanada
CyramzaSolution10 mg/1mLIntravenousEli Lilly and Company2014-04-21Not applicableUs
CyramzaSolution10 mg/1mLIntravenousEli Lilly and Company2014-04-21Not applicableUs
Categories
UNII
D99YVK4L0X
CAS number
947687-13-0

Pharmacology

Indication

For use in advanced gastric or gastro-esophageal junction adenocarcinoma as a single agent or in combination with paclitaxel after prior fluoropyrimidine- or platinum-containing chemotherapy.

Associated Conditions
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.

TargetActionsOrganism
AVascular endothelial growth factor receptor 2
antagonist
Human
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

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.

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

Interactions

Drug Interactions
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Ramucirumab.
AbituzumabThe risk or severity of adverse effects can be increased when Ramucirumab is combined with Abituzumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Ramucirumab.
AdecatumumabThe risk or severity of adverse effects can be increased when Adecatumumab is combined with Ramucirumab.
AducanumabThe risk or severity of adverse effects can be increased when Ramucirumab is combined with Aducanumab.
AfelimomabThe risk or severity of adverse effects can be increased when Afelimomab is combined with Ramucirumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Ramucirumab.
AlirocumabThe risk or severity of adverse effects can be increased when Ramucirumab is combined with Alirocumab.
AmatuximabThe risk or severity of adverse effects can be increased when Ramucirumab is combined with Amatuximab.
AMG 108The risk or severity of adverse effects can be increased when AMG 108 is combined with Ramucirumab.
Food Interactions
Not Available

References

Synthesis Reference

http://www.ema.europa.eu/docs/enGB/documentlibrary/EPAR-Publicassessmentreport/human/002829/WC500180726.pdf

General References
  1. 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. [PubMed:26048277]
  2. 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. [PubMed:25378934]
  3. 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. [PubMed:25281695]
  4. 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. [PubMed:24277700]
  5. Goodkin R, Zaias B, Michelsen WJ: Arteriovenous malformation and glioma: coexistent or sequential? Case report. J Neurosurg. 1990 May;72(5):798-805. [PubMed:2182794]
  6. 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. [PubMed:19636328]
  7. 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. [PubMed:20048182]
  8. 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. [PubMed:11774295]
External Links
KEGG Drug
D09371
PubChem Substance
347910183
ChEMBL
CHEMBL1743062
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Ramucirumab
ATC Codes
L01XC21 — Ramucirumab
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (493 KB)
MSDS
Download (206 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentAdenocarcinomas of the Gastroesophageal Junction / Biliary Tract Cancer / Gastric Adenocarcinoma / Lung Cancer Non-Small Cell Cancer (NSCLC) / Transitional Cell Carcinoma1
1Active Not RecruitingTreatmentAdenocarcinomas of the Gastroesophageal Junction / Hepatocellular,Carcinoma / Lung Cancer Non-Small Cell Cancer (NSCLC) / Malignant Neoplasm of Stomach1
1Active Not RecruitingTreatmentCancer, Advanced / Colorectal Cancers / Mantle Cell Lymphoma (MCL)1
1Active Not RecruitingTreatmentGastro-esophageal Junction Adenocarcinoma / Hepatocellular,Carcinoma / Tumors, Solid1
1Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1Active Not RecruitingTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
1CompletedNot AvailableAdvanced Solid Tumors1
1CompletedTreatmentAdenocarcinomas1
1CompletedTreatmentAdvanced Solid Tumors1
1CompletedTreatmentCancer, Breast / Metastatic Breast Cancer (MBC)1
1CompletedTreatmentCarcinoma, Colorectal1
1CompletedTreatmentHepatocellular,Carcinoma1
1CompletedTreatmentMalignancies2
1CompletedTreatmentStomach Neoplasms1
1CompletedTreatmentTumors, Solid1
1RecruitingTreatmentBreast Cancer (HR+HER2-) / Cutaneous Melanoma / Malignant Neoplasm of Pancreas / Microsatellite Instability-High (MSI-H) Solid Tumors / Tumors, Solid1
1RecruitingTreatmentCentral nervous system neoplasms malignant NEC / Pediatric Solid Tumors / Recurrent Tumor / Refractory Tumors1
1RecruitingTreatmentEsophageal Cancers / Gastro-esophageal Cancer / Malignant Neoplasm of Stomach1
1RecruitingTreatmentEsophagogastric Adenocarcinoma1
1, 2Active Not RecruitingTreatmentAdenocarcinomas of the Gastroesophageal Junction / Cancer, Advanced / Gastric Adenocarcinoma / Hepatocellular Cancer / Lung Cancer Non-Small Cell Cancer (NSCLC) / Renal Cell Adenocarcinoma1
1, 2Not Yet RecruitingTreatmentHead and Neck Squamous Cell Carcinoma (HNSCC)1
1, 2RecruitingTreatmentAdenocarcinomas of the Gastroesophageal Junction / Advanced Gastric Cancer / Metastatic Malignant Neoplasm in the Lymph Nodes / Recurrent Gastric Carcinoma / Stage IV Gastric Cancer AJCC v71
1, 2RecruitingTreatmentGastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma1
1, 2RecruitingTreatmentGastroesophageal Junction Region (GEJ) Cancer / Malignant Neoplasm of Stomach1
2Active Not RecruitingTreatmentAdenocarcinomas of the Gastroesophageal Junction / Gastric Adenocarcinoma2
2Active Not RecruitingTreatmentAdenocarcinomas of the Gastroesophageal Junction / Metastatic Gastric Adenocarcinoma1
2Active Not RecruitingTreatmentBiliary Tract Cancer / Cancer, Advanced / Metastatic Cancers1
2Active Not RecruitingTreatmentColorectal Cancers1
2Active Not RecruitingTreatmentGastroesophageal Junction Cancer / Malignant Neoplasm of Stomach1
2Active Not RecruitingTreatmentHepatocellular,Carcinoma1
2Active Not RecruitingTreatmentMalignant Solid Tumours1
2Active Not RecruitingTreatmentMesothelioma1
2CompletedNot AvailableMalignancies / Tumors, Solid1
2CompletedTreatmentAdult Glioblastoma Multiforme / Brain and Central Nervous System Tumors1
2CompletedTreatmentCancer of the Ovary / Fallopian Tube Cancer / Primary Peritoneal Carcinoma1
2CompletedTreatmentCancer, Breast2
2CompletedTreatmentCarcinoma of Renal Pelvis / Carcinoma of Ureter / Carcinoma of Urinary Tract / Urethral Carcinoma1
2CompletedTreatmentCarcinoma, Colorectal1
2CompletedTreatmentEsophageal Cancers / Malignant Neoplasm of Stomach1
2CompletedTreatmentHepatocellular,Carcinoma1
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)2
2CompletedTreatmentMalignant Neoplasm of Colon / Rectal Carcinoma1
2CompletedTreatmentMalignant Neoplasm of Stomach1
2CompletedTreatmentMalignant Solid Tumours1
2CompletedTreatmentMetastatic Malignant Melanoma1
2CompletedTreatmentMetastatic Non-Small Cell Lung Cancer1
2CompletedTreatmentMetastatic Renal Cell Carcinoma1
2CompletedTreatmentProstate Cancer1
2CompletedTreatmentTumors, Solid1
2Not Yet RecruitingTreatmentAdenocarcinomas of the Gastroesophageal Junction / Gastric Adenocarcinoma / Malignant Neoplasm of Stomach1
2Not Yet RecruitingTreatmentCancer of the Stomach / Gastroesophageal Junction / Malignant Neoplasm of Stomach1
2Not Yet RecruitingTreatmentColorectal Cancers1
2Not Yet RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)2
2RecruitingTreatmentAdenocarcinomas1
2RecruitingTreatmentAdenocarcinomas of the Gastroesophageal Junction / Gastric Adenocarcinoma1
2RecruitingTreatmentAdvanced Gastric or EGJ Cancer1
2RecruitingTreatmentBiliary Cancer1
2RecruitingTreatmentCarcinoid Tumors1
2RecruitingTreatmentGastric Adenocarcinoma / Gastro-esophageal Junction Adenocarcinoma1
2RecruitingTreatmentGastrooesophageal Cancer1
2RecruitingTreatmentLocally Advanced Thymic Carcinoma / Metastatic Thymic Carcinoma / Recurrent Thymic Carcinoma / Unresectable Thymic Carcinoma1
2RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2RecruitingTreatmentMalignant Neoplasm of Pancreas1
2RecruitingTreatmentMesothelioma, Malignant1
2WithdrawnTreatmentStage IV Non-Small Cell Lung Cancer1
2, 3RecruitingTreatmentGastroesophageal Junction Cancer / Malignant Neoplasm of Stomach1
3Active Not RecruitingTreatmentAdenocarcinomas of the Gastroesophageal Junction / Metastatic Gastric Adenocarcinoma1
3Active Not RecruitingTreatmentCancer, Breast1
3Active Not RecruitingTreatmentMetastatic Non-Small Cell Lung Cancer1
3Active Not RecruitingTreatmentTransitional Cell Carcinoma1
3CompletedTreatmentAdenocarcinomas / Malignant Neoplasm of Stomach1
3CompletedTreatmentColorectal Cancers1
3CompletedTreatmentHepatocellular,Carcinoma1
3CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
3CompletedTreatmentMalignant Neoplasm of Stomach1
3RecruitingTreatmentAdenocarcinomas of the Gastroesophageal Junction / Gastric Adenocarcinoma1
3RecruitingTreatmentHepatocellular,Carcinoma1
3RecruitingTreatmentStomach Neoplasms1
Not AvailableNo Longer AvailableNot AvailableAdenocarcinomas of the Gastroesophageal Junction / Malignant Neoplasm of Stomach1
Not AvailableNo Longer AvailableNot AvailableMetastatic Adenocarcinoma of the Gastroesophageal Junction / Metastatic Gastric Cancers1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SolutionIntravenous10 mg
SolutionIntravenous10 mg/1mL
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US2013067098No2011-11-022031-11-02Us

Properties

State
Solid
Experimental Properties
Not Available

Taxonomy

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

Targets

Kind
Protein
Organism
Human
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
  1. Goodkin R, Zaias B, Michelsen WJ: Arteriovenous malformation and glioma: coexistent or sequential? Case report. J Neurosurg. 1990 May;72(5):798-805. [PubMed:2182794]

Drug created on November 18, 2007 11:26 / Updated on November 13, 2018 08:00