Avelumab
Identification
- Name
- Avelumab
- Accession Number
- DB11945
- Description
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
- Not Available
Pharmacology
- Indication
Indicated for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC).
- Associated Conditions
- Locally advanced disease has progressed during or following platinum-containing chemotherapy urothelial carcinoma (UC)
- Locally advanced disease has progressed within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy urothelial carcinoma (UC)
- Metastatic Merkel Cell Carcinoma (MCC)
- Metastatic disease has progressed during or following platinum-containing chemotherapy urothelial carcinoma (UC)
- Metastatic disease has progressed within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy urothelial carcinoma (UC)
- Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More- 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
Learn about our commercial Adverse Effects data.
Learn More- 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.
- Affected organisms
- Humans and other mammals
- 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 Unlock Additional DataAbciximab 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. 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. 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. Antithymocyte immunoglobulin (rabbit) The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Avelumab. Asfotase alfa The risk or severity of adverse effects can be increased when Asfotase alfa is combined with Avelumab. Atezolizumab The risk or severity of adverse effects can be increased when Atezolizumab is combined with Avelumab. Additional Data Available- Extended DescriptionExtended DescriptionAvailable for Purchase
Extended description of the mechanism of action and particular properties of each drug interaction.
Learn more - SeveritySeverityAvailable for Purchase
A severity rating for each drug interaction, from minor to major.
Learn more - Evidence LevelEvidence LevelAvailable for Purchase
A rating for the strength of the evidence supporting each drug interaction.
Learn more - ActionActionAvailable for Purchase
An effect category for each drug interaction. Know how this interaction affects the subject drug.
Learn more
- Food Interactions
- Not Available
Products
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Unlock Additional DataBavencio Injection, solution, concentrate 20 mg/1mL Intravenous EMD Serono, Inc. 2017-03-23 Not applicable US Bavencio Solution 20 mg Intravenous Emd Serono, A Division Of Emd Inc., Canada 2017-12-18 Not applicable Canada Bavencio Injection, solution, concentrate Intravenous Merck Europe B.V. 2017-09-18 Not applicable EU Additional Data Available- Application NumberApplication NumberAvailable for Purchase
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
Learn more - Product CodeProduct CodeAvailable for Purchase
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
Learn more
Categories
- ATC Codes
- L01XC31 — Avelumab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antineoplastic Agents
- 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
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. [PubMed:23724846]
- 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. [PubMed:26014098]
- 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. [PubMed:28373007]
- 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. [PubMed:27592805]
- 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. [PubMed:28274143]
- 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. [PubMed:28375787]
- 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. [PubMed:28165004]
- Merck-Pfizer Alliance: Avelumab Fact Sheet [Link]
- IMGT/mAb-DB card: Avelumab [Link]
- External Links
- AHFS Codes
- 10:00.00 — Antineoplastic Agents
- FDA label
- Download (489 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 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 2 3 Active Not Recruiting Treatment Renal Cell Adenocarcinoma 1 3 Active Not Recruiting Treatment Triple Negative Breast Neoplasms 1 3 Active Not Recruiting Treatment Unresectable, Locally Advanced or Metastatic, Adenocarcinoma of the Stomach, or of the Gastro Esophageal Junction 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 Injection, solution, concentrate Intravenous 20 mg/1mL Injection, solution, concentrate Intravenous; Parenteral 20 MG/ML Injection, solution 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. [PubMed:23724846]
Drug created on October 20, 2016 15:03 / Updated on January 25, 2021 22:38