IMGT/mAb-DB card

Version: 2.0.4 (2023-04-14)

Citing IMGT/mAb-DB

Manso T., Kushwaha A., Abdollahi N., Duroux P., Giudicelli V. and Kossida S. Mechanisms of action of monoclonal antibodies in oncology integrated in IMGT/mAb-DB. Front Immunol., 14 (2023). DOI 10.3389/fimmu.2023.1129323

Poiron C., Wu Y., Ginestoux C., Ehrenmann, Duroux P. and Lefranc M.-P. IMGT/mAb-DB: the IMGT® database for therapeutic monoclonal antibodies. JOBIM 2010, Paper 13 (2010). Abstract

Cambon M., Cherouali K., Kushwaha A., Giudicelli V., Duroux P., Kossida S. and Lefranc M.-P. IMGT/mAb-DB and IMGT/2Dstructure-DB for IMGT standard definition of an antibody: from receptor to amino acid changes. JOBIM 2018, Poster 201 (2018). Abstract

IMGT/mAb-DB ID	512
INN	avelumab
INN Number	10062
INN Prop. List	113 (2015)
INN Rec. List	75 (2016)
Common name	MSB0010718C, MSB-0010718C, MSB0010682
Proprietary name	BAVENCIO®
Species	Homo sapiens
IMGT receptor type	IG
Format (legend)
Receptor identification	IgG1 - lambda
Radiolabelled / Conjugated / Fused
IMGT/2Dstructure-DB	10062
IMGT/3Dstructure-DB	5grj
Specificity target name and species	CD274 (programmed cell death 1 ligand 1, B7H1, B7-H1, PDL1, PD-L1, PDCD1L1, B7 homolog 1, B7 homologue 1) [Homo sapiens]
Development Technology	Human antibody phage display library
Origin clone species
Origin clone name

Company	Merck Serono International S.A. (Geneva Switzerland)
Expression system
Application	Therapeutic
Clinical domain	Oncology
Mechanism of action	Blocking Immunostimulant, Fc-effector function
Clinical indication	Carcinoma, urothelial
Development status	Phase M
Regulatory agency status and year	FDA approval June 30, 2020

Company	Merck Serono International S.A. (Geneva Switzerland)
Expression system
Application	Therapeutic
Clinical domain	Oncology
Mechanism of action	Blocking Immunostimulant, Fc-effector function
Clinical indication	Renal Cell Carcinoma (RCC), advanced
Development status
Regulatory agency status and year

Company	Merck Serono International S.A. (Geneva Switzerland); Pfizer (New York NY USA)
Expression system
Application	Therapeutic
Clinical domain	Oncology
Mechanism of action	Blocking Immunostimulant, Fc-effector function
Clinical indication	Cancers, ovarian
Development status	Phase III
Regulatory agency status and year

Company	Merck Serono International S.A. (Geneva Switzerland); Pfizer (New York NY USA)
Expression system
Application	Therapeutic
Clinical domain	Oncology
Mechanism of action	Blocking Immunostimulant, Fc-effector function
Clinical indication	Cancers, gastric
Development status	Phase III
Regulatory agency status and year	Orphan drug (EMA designation) December 12, 2016

Company	Merck Serono International S.A. (Geneva Switzerland); Pfizer (New York NY USA)
Expression system	CHO (Chinese Hamster Ovary) cells
Application	Therapeutic
Clinical domain	Oncology
Mechanism of action	Blocking Immunostimulant, Fc-effector function
Clinical indication	Cancers, non-small cell lung (NSCLC), metastatic
Development status	Phase III
Regulatory agency status and year

Company	Merck Serono International S.A. (Geneva Switzerland); Pfizer (New York NY USA)
Expression system
Application	Therapeutic
Clinical domain	Oncology
Mechanism of action	Blocking Immunostimulant, Fc-effector function
Clinical indication	Solid tumors
Development status	Phase I
Regulatory agency status and year

Company	Merck Serono International S.A. (Geneva Switzerland); Pfizer (New York NY USA)
Expression system
Application	Therapeutic
Clinical domain	Oncology
Mechanism of action	Blocking Immunostimulant, Fc-effector function
Clinical indication	Merkel cell carcinoma (MCC), metastatic
Development status	Phase M
Regulatory agency status and year	EMA approval August 31, 2020 FDA approval March 23, 2017

Company	Pfizer (New York NY USA)
Expression system
Application	Therapeutic
Clinical domain	Oncology
Mechanism of action	Blocking Immunostimulant, Fc-effector function
Clinical indication	Renal Cell Carcinoma (RCC), advanced
Development status	Phase M
Regulatory agency status and year	FDA approval (in combination with axitinib) May 14, 2019

Clinical trials	211 studies found, 106 recruiting
Authority decisions	EMA: EMEA/H/C/004338 FDA: (BLA) 761049
External links	Kyowa Hakko Kirin: (BLA) 761154
IMGT notes	Phase III for Non-small cell lung cancers (NSCLC) initiated by Merck KGaA, Darmstadt, Germany, and Pfizer. There are four amino acid differences (three of them linked to allotypes and one engineered to the fusion in 10665) between the H chains of 10062 (avelumab) (AA 1-450) Gm17,1, CH1 K120 (217), CH3 D12 (359), L14 (361), CHS K2 (450) and 10665 (bintrafusp alfa) (AA 1-450, not including the fused linker and TGFBR2) Gm3, nG1m1, CH1 R120 (217), CH3 E12 (359), M14 (361), CHS A2 (engineered). The sequence of the amino acids 1-223 of the Fab 3D 4nki_H chain is identical in 10062 and 10665. The amino acid sequence of the lambda chain (1-216 AA) is identical in 10062, in 10665 and in the Fab 3D 4nki_L chain.
Biosimilars

Clinical domain	Oncology
Mechanism of action	Blocking
Effects	Immunostimulant, Fc-effector function
Partners	PDCD1 (programmed cell death 1, PD1, PD-1, CD279)
Schema
Description	Avelumab targets and binds to programmed cell death ligand 1 (CD274,PD-L1), an immunosuppressive ligand expressed on tumor cells that downregulates both activation and proliferation of T cells. Once bound to CD274, avelumab blocks its binding to its receptor programmed cell death 1 (PDCD1, PD-1) expressed on activated T cells, leaving the PDCD1 pathway intact through its second ligand, PDCD1LG2 (PD-L2), which is less expressed in tumor cells, to maintain inhibitory signals mediated by PDCD1LG2/PDCD1. This blockade reverses the inactivation of T cells caused by PDCD1 signaling resulting in activation and expansion of T cells as well as enhancement of cytotoxic T lymphocyte (CTL)-mediated anti-tumor immune response against tumor cells. Avelumab is an IgG1-kappa antibody with ability to bind to FcyRIIIa and induce antibody-dependent cell-mediated cytotoxicity (ADCC) for potential enhanced efficacy in certain tumor types.
References	Roviello G, D'Angelo A, Generali D, et al., Immunotherapy. 2019; 11(9):759-768. DOI: 10.2217/imt-2019-0011. PMID: 31060469

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