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
Avelumab is indicated for the treatment of adult and pediatric patients ≥12 years of age with metastatic Merkel cell carcinoma (MCC).10
It is also indicated as maintenance treatment in patients with locally advanced or metastatic urothelial carcinoma (UC) which has not progressed with first-line platinum-containing chemotherapy. In addition, it is indicated in patients with locally advanced or metastatic UC who experience disease progression on or after platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.10
Avelumab is additionally indicated as first-line treatment, in combination with axitinib, in the treatment of advanced renal cell carcinoma (RCC).10
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- Associated Therapies
- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- 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.
Target Actions Organism AProgrammed cell death 1 ligand 1 inhibitorantibodyHumans - 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
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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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Avelumab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Avelumab. Aducanumab The risk or severity of adverse effects can be increased when Avelumab is combined with Aducanumab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Avelumab. Alirocumab The risk or severity of adverse effects can be increased when Alirocumab is combined with Avelumab. Amivantamab The risk or severity of adverse effects can be increased when Avelumab is combined with Amivantamab. Anifrolumab The risk or severity of adverse effects can be increased when Avelumab is combined with Anifrolumab. Ansuvimab The risk or severity of adverse effects can be increased when Avelumab is combined with Ansuvimab. Anthrax immune globulin human The 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. 
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- 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 Bavencio Injection, solution, concentrate 20 mg/1mL Intravenous EMD Serono, Inc. 2017-03-23 Not applicable US 
Bavencio Injection, solution, concentrate 20 mg/mL Intravenous Merck Europe B.V. 2020-12-16 Not applicable EU 
Bavencio Solution 20 mg / mL Intravenous Emd Serono, A Division Of Emd Inc., Canada 2017-12-18 Not applicable Canada 
Categories
- ATC Codes
- L01XC31 — Avelumab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Antineoplastic and Immunomodulating Agents
- Blood Proteins
- Cancer immunotherapy
- Globulins
- Immune Checkpoint Inhibitors
- Immunoglobulins
- Immunoproteins
- Immunotherapy
- Narrow Therapeutic Index Drugs
- Programmed Death Ligand-1 Antagonists
- Programmed Death Ligand-1 Blocker
- Programmed Death Ligand-1-directed Antibody Interactions
- Proteins
- Serum Globulins
- 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
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- Merck-Pfizer Alliance: Avelumab Fact Sheet [Link]
- IMGT/mAb-DB card: Avelumab [Link]
- FDA Approved Drug Products: BAVENCIO (avelumab) injection, for intravenous use [Link]
- External Links
- FDA label
- Download (489 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Breast Neoplasms, Triple-Negative 1 3 Active Not Recruiting Treatment First Line Non-Small Cell Lung Cancer 1 3 Active Not Recruiting Treatment HNSCC 1 3 Active Not Recruiting Treatment Microsatellite Instability / POLE Exonuclease Mutant Colon Cancer / Stage III Colon Cancer 1 3 Active Not Recruiting Treatment Ovarian Cancer 1 3 Active Not Recruiting Treatment Renal Cell Carcinoma 1 3 Active Not Recruiting Treatment Solid Tumors 1 3 Active Not Recruiting Treatment Urothelial Cancer 1 3 Completed Treatment Gastric Cancer Third Line / Unresectable, Recurrent, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma 1 3 Completed Treatment Non-Small Cell Lung Carcinoma (NSCLC) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution, concentrate Intravenous 20 mg/mL Injection, solution, concentrate Intravenous 20 mg/1mL Injection, solution, concentrate Intravenous; Parenteral 20 MG/ML Solution Intravenous 20 mg / mL Injection, solution Intravenous Injection, solution, concentrate Intravenous 200 mg/10ml Solution Intravenous 20 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- InhibitorAntibody
- 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
- 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 at October 20, 2016 21:03 / Updated at June 03, 2022 07:24