Avelumab

Identification

Summary

Avelumab is an anti-PD-L1 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 human IgG1 lambda monoclonal antibody that binds programmed cell death ligand-1 (PD-L1) to block its interaction with its receptors found on T cells and antigen-presenting cells.3 Avelumab was first approved by the FDA on March 23, 2017.3 On September 18 and December 18 of the same year, it was also granted approval by EMA 8 and Health Canada,9 respectively. It is used in the treatment of Merkel cell carcinoma, metastatic urothelial carcinoma, or renal cell carcinoma.

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
C6374H9898N1694O2010S44
Protein Average Weight
147000.0 Da (approximate including glycans)
Sequences
>Heavy chain
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYIMMWVRQAPGKGLEWVSSIYPSGGITFY
ADTVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARIKLGTVTTVDYWGQGTLVTVSS
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS
GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG
PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN
STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDE
LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW
QQGNVFSCSVMHEALHNHYTQKSLSLSPGK
>Light chain
QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSNRPSGV
SNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTRVFGTGTKVTVLGQPKANPTVT
LFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASS
YLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS
References:
  1. KEGG DRUG: Avelumab [Link]
Download FASTA Format
Synonyms
  • Avelumab
External IDs
  • MSB0010718C

Pharmacology

Indication

Avelumab is indicated for the treatment of adults with metastatic Merkel cell carcinoma (MCC).8,9 In the US, it is also used in patients 12 years and older.7

It is also indicated as the maintenance treatment in patients with locally advanced or metastatic urothelial carcinoma (UC), which has not progressed with first-line platinum-containing chemotherapy.6,8,9 In the US, avelumab is also indicated to treat locally advanced or metastatic UC with disease progression during or after platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.6

Avelumab is indicated, in combination with axitinib, for the first-line treatment of advanced renal cell carcinoma (RCC).6

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to treatAdvanced renal cell carcinoma (arcc)Regimen in combination with: Axitinib (DB06626)••••••••••••••••••••• •••••
Treatment ofMetastatic urothelial cancer••••••••••••••••••• ••••••••••• ••••• ••••••••••••••••••• ••••••••••••
Treatment ofMetastatic urothelial cancer•••••••••••••••••••• •••••••••• ••••••••••••• •••••••• •••••••••••••• ••••••••••••
Treatment ofLocally advanced urothelial carcinoma••••••••••••••••••• ••••••••••• ••••• ••••••••••••••••••• ••••••••••••
Treatment ofLocally advanced urothelial carcinoma••••••••••••••••••• ••••••••••• ••••• ••••••••••••••••••• ••••••••••••
Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

Avelumab is an immunotherapeutic and antineoplastic agent belonging to the immune checkpoint blockade cancer therapies group. It induces antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro;1,3,7 however it is unclear whether ADCC contributes to the therapeutic actions of avelumab.3 Avelumab decreased tumour growth in syngeneic mouse tumour models.3,7

Mechanism of action

Programmed death ligand 1 (PD-L1) is a transmembrane protein and a co-inhibitory co-inhibitory immune checkpoint to suppress cytotoxic T-cell activity, proliferation, and cytokine production. It binds to PD receptor-1 (PD-1) and B7.1 receptors expressed on cytotoxic T cells and antigen-presenting cells to mediate its actions. PD-L1 is often expressed in tumours and surrounding tumour-infiltrating immune cells as an adaptive immune mechanism, decreasing the anti-tumour immune response in the tumour microenvironment.2,3,5,7

Avelumab binds PD-L1 and blocks its interaction with its receptors PD-1 and B7.1, disinhibiting PD-L1 effects on tumour-infiltrating lymphocytes and restoring anti-tumor immune responses.3,7

TargetActionsOrganism
AProgrammed cell death 1 ligand 1
inhibitor
antibody
Humans
Absorption

In patients who received doses ranging from 1 to 20 mg/kg every two weeks, avelumab exposure increased dose proportionally in the dose range of 10 to 20 mg/kg. Steady-state concentrations of avelumab were reached after approximately four to six weeks (two to three cycles) of repeated dosing, and the systemic accumulation was approximately 1.25-fold.7

Volume of distribution

The geometric mean volume of distribution at steady state for a subject receiving 10 mg/kg is 4.72 L.7 Avelumab is expected to be distributed in the systemic circulation and, to a lesser extent, in the extracellular space.9

Protein binding

Not Available

Metabolism

Avelumab undergoes nonspecific proteolytic degradation.7

Route of elimination

Not Available

Half-life

The terminal half-life is approximately 6.1 days in patients with solid tumours receiving 10 mg/kg.7

Clearance

The total systemic clearance is approximately 0.59 L/day in patients with solid tumours receiving 10 mg/kg.7

Adverse Effects
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Toxicity

There is limited information regarding the LD50 of avelumab. Three patients who received a dose of avelumab that was 5% to 10% above the recommended dose experienced an overdose: the patients reported no symptoms and continued on avelumab therapy without requiring any treatment for the overdose. In the case of an overdose, patients should be closely monitored for signs or symptoms of adverse reactions. The treatment is directed to the management of symptoms.8

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.
Food Interactions
  • Take with or without food.

Products

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

Categories

ATC Codes
L01FF04 — 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. 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]
  2. 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]
  3. Kim ES: Avelumab: First Global Approval. Drugs. 2017 May;77(8):929-937. doi: 10.1007/s40265-017-0749-6. [Article]
  4. Collins JM, Gulley JL: Product review: avelumab, an anti-PD-L1 antibody. Hum Vaccin Immunother. 2019;15(4):891-908. doi: 10.1080/21645515.2018.1551671. Epub 2018 Dec 20. [Article]
  5. Han Y, Liu D, Li L: PD-1/PD-L1 pathway: current researches in cancer. Am J Cancer Res. 2020 Mar 1;10(3):727-742. eCollection 2020. [Article]
  6. FDA Approved Drug Products: BAVENCIO (avelumab) injection, for intravenous use (November 2020) [Link]
  7. FDA Approved Drug Products: BAVENCIO (avelumab) injection, for intravenous use (September 2023) [Link]
  8. EMA Approved Drug Products: Bavencio (avelumab) Intravenous Infusion [Link]
  9. Health Canada Approved Drug Products: BAVENCIO (Avelumab) injection, for intravenous infusion [Link]
PubChem Substance
347911260
RxNav
1875534
Wikipedia
Avelumab

Clinical Trials

Clinical Trials

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solution, concentrateIntravenous20 mg/1mL
Injection, solution, concentrateIntravenous20 mg/mL
Injection, solution, concentrateIntravenous; Parenteral20 MG/ML
SolutionIntravenous20 mg / mL
SolutionIntravenous200 mg
Injection, solutionIntravenous200 mg/10ml
Injection, solution, concentrateIntravenous200 mg/10ml
SolutionIntravenous20 mg
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Targets

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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]
  2. Kyriakidis I, Vasileiou E, Rossig C, Roilides E, Groll AH, Tragiannidis A: Invasive Fungal Diseases in Children with Hematological Malignancies Treated with Therapies That Target Cell Surface Antigens: Monoclonal Antibodies, Immune Checkpoint Inhibitors and CAR T-Cell Therapies. J Fungi (Basel). 2021 Mar 5;7(3). pii: jof7030186. doi: 10.3390/jof7030186. [Article]
  3. FDA Approved Drug Products: BAVENCIO (avelumab) injection, for intravenous use (September 2023) [Link]

Drug created at October 20, 2016 21:03 / Updated at November 20, 2023 20:11