Identification

Name
Avelumab
Accession Number
DB11945
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
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.

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
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BavencioInjection, solution, concentrate20 mg/mLIntravenousEmd Serono2017-03-23Not applicableUs
Categories
UNII
KXG2PJ551I
CAS number
1537032-82-8

Pharmacology

Indication

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

Structured Indications
Not Available
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
antagonist
Human
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.

Toxicity

The most common serious adverse reactions to avelumab are immune-mediated adverse reactions (pneumonitis, hepatitis, colitis, adrenal insufficiency, hypo- and hyperthyroidism, diabetes mellitus, and nephritis) and life-threatening infusion reactions. 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
DrugInteractionDrug group
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Avelumab.Investigational
Clostridium tetani toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Clostridium tetani toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Avelumab.Approved
Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Avelumab.Approved
G17DTThe therapeutic efficacy of G17DT can be decreased when used in combination with Avelumab.Investigational
GI-5005The therapeutic efficacy of GI-5005 can be decreased when used in combination with Avelumab.Investigational
Hepatitis A VaccineThe therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Avelumab.Approved
Hepatitis B Vaccine (Recombinant)The therapeutic efficacy of Hepatitis B Vaccine (Recombinant) can be decreased when used in combination with Avelumab.Approved, Withdrawn
INGN 201The therapeutic efficacy of INGN 201 can be decreased when used in combination with Avelumab.Investigational
INGN 225The therapeutic efficacy of INGN 225 can be decreased when used in combination with Avelumab.Investigational
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Avelumab.Approved
RindopepimutThe therapeutic efficacy of Rindopepimut can be decreased when used in combination with Avelumab.Investigational
Rotavirus VaccineThe therapeutic efficacy of Rotavirus Vaccine can be decreased when used in combination with Avelumab.Approved
Rubella virus vaccineThe therapeutic efficacy of Rubella virus vaccine can be decreased when used in combination with Avelumab.Approved
Salmonella typhi ty21a live antigenThe therapeutic efficacy of Salmonella typhi ty21a live antigen can be decreased when used in combination with Avelumab.Approved
SRP 299The therapeutic efficacy of SRP 299 can be decreased when used in combination with Avelumab.Investigational
TecemotideThe therapeutic efficacy of Tecemotide can be decreased when used in combination with Avelumab.Investigational
TG4010The therapeutic efficacy of TG4010 can be decreased when used in combination with Avelumab.Investigational
Yellow fever vaccineThe therapeutic efficacy of Yellow fever vaccine can be decreased when used in combination with Avelumab.Approved
Zoster vaccineThe therapeutic efficacy of Zoster vaccine can be decreased when used in combination with Avelumab.Approved
Food Interactions
Not Available

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. [PubMed:23724846]
  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. [PubMed:26014098]
  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. [PubMed:28373007]
  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. [PubMed:27592805]
  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. [PubMed:28274143]
  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. [PubMed:28375787]
  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. [PubMed:28165004]
  8. Merck-Pfizer Alliance: Avelumab Fact Sheet [Link]
  9. IMGT/mAb-DB card: Avelumab [Link]
External Links
PubChem Substance
347911260
FDA label
Download (489 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentLymphomas non-Hodgkin's B-cell1
0RecruitingTreatmentMetastatic Non-Small Cell Lung Cancer1
1Active Not RecruitingTreatmentRenal Cell Adenocarcinoma1
1Active Not RecruitingTreatmentTumors, Solid1
1Not Yet RecruitingTreatmentMeningioma, Adult / Meningiomas1
1Not Yet RecruitingTreatmentRenal Cell Adenocarcinoma1
1RecruitingTreatmentAdenocarcinomas1
1RecruitingTreatmentAdvanced Solid Tumors1
1RecruitingTreatmentCarcinoma, Squamous Cell of Head and Neck1
1RecruitingTreatmentHepatocellular,Carcinoma1
1RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Neoplasms1
1RecruitingTreatmentLymphoma, Hodgkins1
1RecruitingTreatmentTumors, Solid1
1, 2Not Yet RecruitingTreatmentCancer, Ovarian1
1, 2Not Yet RecruitingTreatmentCarcinoma, Colorectal1
1, 2Not Yet RecruitingTreatmentColorectal Cancers1
1, 2Not Yet RecruitingTreatmentHead and Neck Squamous Cell Carcinoma (HNSCC)1
1, 2Not Yet RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2Not Yet RecruitingTreatmentMelanoma1
1, 2Not Yet RecruitingTreatmentNeuroendocrine Carcinoma of the Skin1
1, 2Not Yet RecruitingTreatmentNeuroendocrine Carcinomas1
1, 2Not Yet RecruitingTreatmentNon Hodgkin Lymphoma (NHL)1
1, 2Not Yet RecruitingTreatmentTransitional Cell Carcinoma1
1, 2Not Yet RecruitingTreatmentTriple Negative Breast Cancer (TNBC)1
1, 2RecruitingTreatmentEarly Stage Non-small Cell Lung Cancer1
1, 2RecruitingTreatmentFallopian Tube Cancer / Malignant Peritoneal Neoplasm / Ovarian Epithelial Cancer1
1, 2RecruitingTreatmentHead and Neck Squamous Cell Carcinoma (HNSCC) / HPV Positive Oropharyngeal Squamous Cell Carcinoma / HPV-Related Carcinoma1
1, 2RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML) / Refractory Acute Myeloid Leukemia / Relapsed Acute Myeloid Leukemia1
1, 2RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2RecruitingTreatmentMalignant Neoplasm of Breast / Malignant Neoplasms of Bone and Articular Cartilage / Malignant Neoplasms of Digestive Organs / Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System / Malignant Neoplasms of Female Genital Organs / Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites / Malignant Neoplasms of Independent (Primary) Multiple Sites / Malignant Neoplasms of Lip Oral Cavity and Pharynx / Malignant Neoplasms of Male Genital Organs / Malignant Neoplasms of Mesothelial and Soft Tissue / Malignant Neoplasms of Respiratory and Intrathoracic Organs / Malignant Neoplasms of Thyroid and Other Endocrine Glands / Malignant Neoplasms of Urinary Tract / Neoplasms of Uncertain or Unknown Behavior1
1, 2RecruitingTreatmentMalignant Neoplasm of Pancreas2
1, 2RecruitingTreatmentMerkel Cell Polyomavirus Infection / Stage IV Merkel Cell Carcinoma / Stage IV Merkel Cell Carcinoma AJCC v71
1, 2RecruitingTreatmentMetastatic Leiomyosarcoma / Metastatic Liposarcoma1
2Not Yet RecruitingTreatmentAdenocarcinoma Of Esophagus / Gastric Adenocarcinoma1
2Not Yet RecruitingTreatmentBladder Carcinoma1
2Not Yet RecruitingTreatmentMetastatic Colorectal Cancers / MSI1
2Not Yet RecruitingTreatmentMetastatic Colorectal Cancers1
2Not Yet RecruitingTreatmentNeuroendocrine Carcinoma, Grade 31
2Not Yet RecruitingTreatmentNeuroendocrine Tumors1
2Not Yet RecruitingTreatmentProstate Cancer1
2Not Yet RecruitingTreatmentRectal Carcinoma1
2Not Yet RecruitingTreatmentRecurrent Ovarian, Peritoneal and Fallopian Tube Cancer (ROPT)1
2Not Yet RecruitingTreatmentT-cell lymphoma refractory / T-Cell Lymphoma Relapsed1
2RecruitingTreatmentCancer, Advanced1
2RecruitingTreatmentClear Cell Renal Cell Carcinoma / Clear-cell Kidney Carcinoma / RCC / Renal Cancers1
2RecruitingTreatmentColorectal Cancers1
2RecruitingTreatmentGestational Trophoblastic Neoplasias (GTN)1
2RecruitingTreatmentGlioblastoma Multiforme of Brain1
2RecruitingTreatmentGlioblastomas1
2RecruitingTreatmentHuman Papilloma Virus (HPV) / Juvenile Laryngeal Papilloma / Laryngeal Papilloma, Recurrent / Recurrent Respiratory Papillomatosis / Respiratory Papillomatosis1
2RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)2
2RecruitingTreatmentMalignant Neoplasm of Nasopharynx1
2RecruitingTreatmentMetastatic Breast Cancer (MBC)1
2RecruitingTreatmentMetastatic Colorectal Cancers1
2RecruitingTreatmentMicrosatellite Stable Relapsed or Refractory Colorectal Cancer1
2RecruitingTreatmentNeuroendocrine Carcinoma of the Skin1
2RecruitingTreatmentRecurrent Glioblastoma (WHO-Grade IV Glioma)1
2RecruitingTreatmentSarcoma, Osteogenic1
2RecruitingTreatmentAdvanced thymic carcinoma / Thymic Carcinoma1
2RecruitingTreatmentMetastatic Endometrial cancer1
3Active Not RecruitingTreatmentCancer, Ovarian1
3Active Not RecruitingTreatmentGastric Cancer Third Line / Unresectable, Recurrent, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma1
3Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
3Not Yet RecruitingTreatmentHNSCC1
3Not Yet RecruitingTreatmentStage III Merkel Cell Carcinoma / Stage IIIB Merkel Cell Carcinoma1
3RecruitingTreatmentCancer, Ovarian1
3RecruitingTreatmentFirst Line Non-Small Cell Lung Cancer1
3RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
3RecruitingTreatmentRenal Cell Adenocarcinoma1
3RecruitingTreatmentSquamous Cell Carcinoma of the Head and Neck (SCCHN)1
3RecruitingTreatmentTriple Negative Breast Neoplasms1
3RecruitingTreatmentUnresectable, Locally Advanced or Metastatic, Adenocarcinoma of the Stomach, or of the Gastro Esophageal Junction1
3RecruitingTreatmentUrothelial Cancer1
Not AvailableAvailableNot AvailableMetastatic Merkel Cell Carcinoma1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solution, concentrateIntravenous20 mg/mL
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
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
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. [PubMed:23724846]

Drug created on October 20, 2016 15:03 / Updated on November 06, 2017 06:46