Avelumab

Identification

Summary

Avelumab is a monoclonal antibody used to treat metastatic merkel cell carcinoma, metastatic urothelial carcinoma, or renal cell carcinoma.

Brand Names
Bavencio
Generic Name
Avelumab
DrugBank Accession Number
DB11945
Background

Avelumab is a programmed death ligand-1 (PD-L1) blocking antibody indicated for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC). It is a fully human anti-PD immunoglobulin G1 (IgG1) lambda monoclonal antibody with antineoplastic actions. It was granted accelerated approval in March 2017 under the name Bavencio.

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
C6374H9898N1694O2010S44
Protein Average Weight
142.0 Da (approximate including glycans)
Sequences
>Heavy chain
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYIMMWVRQAPGKGLEWVSSIYPSGGITFY
ADTVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARIKLGTVTTVDYWGQGTLVTVSS
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS
GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG
PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN
STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDE
LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW
QQGNVFSCSVMHEALHNHYTQKSLSLSPGK
>Light chain
QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSNRPSGV
SNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTRVFGTGTKVTVLGQPKANPTVT
LFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASS
YLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS
Download FASTA Format
Synonyms
  • Avelumab

Pharmacology

Indication

Indicated for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC).

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Avelumab is a whole antibody that binds the immunosuppressive programmed death-ligand 1 and inhibits the interaction between PD-1 and PD-L1. It prevents the formation of a PD-1/PD-L1 receptor/ligand complex that normally leads to inhibition of CD8+ T cells, and therefore inhibition of an immune reaction. Alevumab is an immunotherapeutic and antineoplastic agent that belongs to the group of immune checkpoint blockade cancer therapies. By retaining a native Fc-region, avelumab is thought to engage the innate immune system and may induce antibody-dependent cell-mediated cytotoxicity (ADCC).

Mechanism of action

PD-L1 may be expressed on tumor cells and tumor-infiltrating immune cells and can contribute to the inhibition of the anti-tumor immune response in the tumor microenvironment. Binding of PD-L1 to the PD-1 and B7.1 receptors found on T cells and antigen presenting cells suppresses cytotoxic T-cell activity, T-cell proliferation and cytokine production. Avelumab binds PD-L1 through the FG loops 7 and blocks the interaction between PD-L1 and its receptors PD-1 and B7.1. This interaction releases the inhibitory effects of PD-L1 on the immune response resulting in the restoration of immune responses, including anti-tumor immune responses. Avelumab has also been shown to induce antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro. In syngeneic mouse tumor models, blocking PD-L1 activity resulted in decreased tumor growth.

TargetActionsOrganism
AProgrammed cell death 1 ligand 1
inhibitor
antibody
Humans
Absorption

The exposure of avelumab increased dose-proportionally in the dose range of 10 to 20 mg/kg every 2 weeks. Steady-state concentrations of avelumab were reached after approximately 4 to 6 weeks (2 to 3 cycles) of repeated dosing, and the systemic accumulation was approximately 1.25-fold.

Volume of distribution

The geometric mean volume of distribution at steady state for a subject receiving 10 mg/kg is 4.72 L.

Protein binding

None reported.

Metabolism

Avelumab undergoes nonspecific proteolytic degradation.

Route of elimination

Mainly eliminated through proteolytic degradation.

Half-life

The terminal half-life is approximately 6.1 days in patients receiving 10 mg/kg.

Clearance

The total systemic clearance is approximately 0.59 L/day.

Adverse Effects
Adverseeffects
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Toxicity

Avelumab toxicity includes the possibility of experiencing potentially fatal infusion reactions and/or immunogenic reactions like pneumonitis, hepatitis, colitis, adrenal insufficiency, hypo- and hyperthyroidism, diabetes mellitus, and nephritis, among others. Other common adverse effects include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, rash, decreased appetite, and peripheral edema.

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 Avelumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Avelumab.
AducanumabThe risk or severity of adverse effects can be increased when Avelumab is combined with Aducanumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Avelumab.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Avelumab.
AmivantamabThe risk or severity of adverse effects can be increased when Avelumab is combined with Amivantamab.
AnifrolumabThe risk or severity of adverse effects can be increased when Avelumab is combined with Anifrolumab.
AnsuvimabThe risk or severity of adverse effects can be increased when Avelumab is combined with Ansuvimab.
Anthrax immune globulin humanThe risk or severity of adverse effects can be increased when Anthrax immune globulin human is combined with Avelumab.
Antilymphocyte immunoglobulin (horse)The risk or severity of adverse effects can be increased when Antilymphocyte immunoglobulin (horse) is combined with Avelumab.
Interactions
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Food Interactions
No interactions found.

Products

Products2
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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
BavencioInjection, solution, concentrate20 mg/1mLIntravenousEMD Serono, Inc.2017-03-23Not applicableUS flag
BavencioSolution20 mg / mLIntravenousEmd Serono, A Division Of Emd Inc., Canada2017-12-18Not applicableCanada flag
BavencioInjection, solution, concentrate20 mg/mLIntravenousMerck Europe B.V.2020-12-16Not applicableEU flag

Categories

ATC Codes
L01XC31 — Avelumab
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
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
KXG2PJ551I
CAS number
1537032-82-8

References

General References
  1. Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, Wolchok JD, Hersey P, Joseph RW, Weber JS, Dronca R, Gangadhar TC, Patnaik A, Zarour H, Joshua AM, Gergich K, Elassaiss-Schaap J, Algazi A, Mateus C, Boasberg P, Tumeh PC, Chmielowski B, Ebbinghaus SW, Li XN, Kang SP, Ribas A: Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013 Jul 11;369(2):134-44. doi: 10.1056/NEJMoa1305133. Epub 2013 Jun 2. [Article]
  2. Boyerinas B, Jochems C, Fantini M, Heery CR, Gulley JL, Tsang KY, Schlom J: Antibody-Dependent Cellular Cytotoxicity Activity of a Novel Anti-PD-L1 Antibody Avelumab (MSB0010718C) on Human Tumor Cells. Cancer Immunol Res. 2015 Oct;3(10):1148-57. doi: 10.1158/2326-6066.CIR-15-0059. Epub 2015 May 26. [Article]
  3. Heery CR, O'Sullivan-Coyne G, Madan RA, Cordes L, Rajan A, Rauckhorst M, Lamping E, Oyelakin I, Marte JL, Lepone LM, Donahue RN, Grenga I, Cuillerot JM, Neuteboom B, Heydebreck AV, Chin K, Schlom J, Gulley JL: Avelumab for metastatic or locally advanced previously treated solid tumours (JAVELIN Solid Tumor): a phase 1a, multicohort, dose-escalation trial. Lancet Oncol. 2017 May;18(5):587-598. doi: 10.1016/S1470-2045(17)30239-5. Epub 2017 Mar 31. [Article]
  4. Kaufman HL, Russell J, Hamid O, Bhatia S, Terheyden P, D'Angelo SP, Shih KC, Lebbe C, Linette GP, Milella M, Brownell I, Lewis KD, Lorch JH, Chin K, Mahnke L, von Heydebreck A, Cuillerot JM, Nghiem P: Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. Lancet Oncol. 2016 Oct;17(10):1374-1385. doi: 10.1016/S1470-2045(16)30364-3. Epub 2016 Sep 1. [Article]
  5. Hamilton G, Rath B: Avelumab: combining immune checkpoint inhibition and antibody-dependent cytotoxicity. Expert Opin Biol Ther. 2017 Apr;17(4):515-523. doi: 10.1080/14712598.2017.1294156. Epub 2017 Feb 22. [Article]
  6. Apolo AB, Infante JR, Balmanoukian A, Patel MR, Wang D, Kelly K, Mega AE, Britten CD, Ravaud A, Mita AC, Safran H, Stinchcombe TE, Srdanov M, Gelb AB, Schlichting M, Chin K, Gulley JL: Avelumab, an Anti-Programmed Death-Ligand 1 Antibody, In Patients With Refractory Metastatic Urothelial Carcinoma: Results From a Multicenter, Phase Ib Study. J Clin Oncol. 2017 Apr 4:JCO2016716795. doi: 10.1200/JCO.2016.71.6795. [Article]
  7. Tan S, Zhang H, Chai Y, Song H, Tong Z, Wang Q, Qi J, Wong G, Zhu X, Liu WJ, Gao S, Wang Z, Shi Y, Yang F, Gao GF, Yan J: An unexpected N-terminal loop in PD-1 dominates binding by nivolumab. Nat Commun. 2017 Feb 6;8:14369. doi: 10.1038/ncomms14369. [Article]
  8. Merck-Pfizer Alliance: Avelumab Fact Sheet [Link]
  9. IMGT/mAb-DB card: Avelumab [Link]
PubChem Substance
347911260
RxNav
1875534
Wikipedia
Avelumab
FDA label
Download (489 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentBreast Neoplasms, Triple-Negative1
3Active Not RecruitingTreatmentFirst Line Non-Small Cell Lung Cancer1
3Active Not RecruitingTreatmentHNSCC1
3Active Not RecruitingTreatmentMicrosatellite Instability / POLE Exonuclease Mutant Colon Cancer / Stage III Colon Cancer1
3Active Not RecruitingTreatmentOvarian Cancer2
3Active Not RecruitingTreatmentRenal Cell Adenocarcinoma1
3Active Not RecruitingTreatmentTumors, Solid1
3Active Not RecruitingTreatmentUrothelial Cancer1
3CompletedTreatmentGastric Cancer Third Line / Unresectable, Recurrent, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma1
3CompletedTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solution, concentrateIntravenous20 mg/mL
Injection, solution, concentrateIntravenous20 mg/1mL
Injection, solution, concentrateIntravenous; Parenteral20 MG/ML
SolutionIntravenous20 mg / mL
Injection, solutionIntravenous
SolutionIntravenous20 mg
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
Antibody
General Function
Not Available
Specific Function
Involved in the costimulatory signal, essential for T-cell proliferation and production of IL10 and IFNG, in an IL2-dependent and a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell ...
Gene Name
CD274
Uniprot ID
Q9NZQ7
Uniprot Name
Programmed cell death 1 ligand 1
Molecular Weight
33275.095 Da
References
  1. Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, Wolchok JD, Hersey P, Joseph RW, Weber JS, Dronca R, Gangadhar TC, Patnaik A, Zarour H, Joshua AM, Gergich K, Elassaiss-Schaap J, Algazi A, Mateus C, Boasberg P, Tumeh PC, Chmielowski B, Ebbinghaus SW, Li XN, Kang SP, Ribas A: Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013 Jul 11;369(2):134-44. doi: 10.1056/NEJMoa1305133. Epub 2013 Jun 2. [Article]

Drug created on October 20, 2016 21:03 / Updated on September 19, 2021 19:53