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Target Overview
NKG2A is an immune checkpoint inhibitor receptor that is expressed on NK cells, as well as tumor-infiltrating CD8+ T cells.1,2 Its natural ligand, HLA-E, is highly expressed on many solid and hematologic tumors.3,4 Binding of tumor-associated HLA-E to NKG2A inhibits NK cell and CD8+ T-cell activation and ablates NK cell and CD8+ T-cell–mediated antitumor killing.5,6
Compound Overview
Monalizumaba is an investigational anti-NKG2A antibody that binds to NKG2A on NK cells and intratumoral CD8+ T cells and helps block the inhibitory interactions between tumor-associated HLA-E and the NKG2A receptor. This, in turn, may enhance innate immune antitumor responses. This molecule is being clinically evaluated in various solid tumors.
aAstraZeneca has a co-development agreement with Innate Pharma to develop monalizumab in oncology.
Mechanism of Action
Reference: Martinez-Marti et al. ESMO 2021 oral presentation (LBA42).
References
1. Platonova S, Cherfils-Vicini J, Damotte D, et al. Cancer Res. 2011;71(16):5412-5422. 2. Sheu B-C, Chiou S-H, Lin H-H, et al. Cancer Res. 2005;65(7):2921-2929. 3. Braud VM, Allan DS, O’Callaghan CA, et al. Nature. 1998;391(6669):795-799. 4. Talebian Yazdi M, van Riet S, van Schadewijk A, et al. Oncotarget. 2016;7(3):3477-3488. 5. Pace E, Di Sano C, Ferraro M, et al. Eur J Cancer. 2011;47(2):296-304. 6. Speiser DE, Pittet MJ, Valmori D, et al. J Exp Med. 1999;190(6):775-782.
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Abbreviations
ADCC
antibody-dependent cellular cytotoxicity
ALK
anaplastic lymphoma kinase
BICR
blinded independent central review
cCRT
concurrent chemoradiation therapy
DoR
duration of response
EGFR
epidermal growth factor receptor
HLA-E
HLA class I histocompatibility antigen E
HNSCC
head and neck squamous cell carcinoma
IV
intravenous
NK
natural killer
NKG2A
natural killer cell lectin-like receptor
NSCLC
non-small cell lung cancer
ORR
overall or objective response rate
OS
overall survival
PD-1
programmed cell death-1
PD-L1
programmed cell death ligand-1
PDC
platinum doublet chemotherapy
PFS
progression-free survival
PFS2
time to second progression or death
Q*W
every * weeks
Q4W
every 4 weeks
R
randomization
RECIST
Response Evaluation Criteria in Solid Tumors
TFST
time to first subsequent therapy
TTDM
time to death or distant metastases
Target Overview
NKG2A is an immune checkpoint inhibitor receptor that is expressed on NK cells, as well as tumor-infiltrating CD8+ T cells.1,2 Its natural ligand, HLA-E, is highly expressed on many solid and hematologic tumors.3,4 Binding of tumor-associated HLA-E to NKG2A inhibits NK cell and CD8+ T-cell activation and ablates NK cell and CD8+ T-cell–mediated antitumor killing.5,6
Compound Overview
Monalizumaba is an investigational anti-NKG2A antibody that binds to NKG2A on NK cells and intratumoral CD8+ T cells and helps block the inhibitory interactions between tumor-associated HLA-E and the NKG2A receptor. This, in turn, may enhance innate immune antitumor responses. This molecule is being clinically evaluated in various solid tumors.
aAstraZeneca has a co-development agreement with Innate Pharma to develop monalizumab in oncology.
Mechanism of Action
Reference: Martinez-Marti et al. ESMO 2021 oral presentation (LBA42).
References
1. Platonova S, Cherfils-Vicini J, Damotte D, et al. Cancer Res. 2011;71(16):5412-5422. 2. Sheu B-C, Chiou S-H, Lin H-H, et al. Cancer Res. 2005;65(7):2921-2929. 3. Braud VM, Allan DS, O’Callaghan CA, et al. Nature. 1998;391(6669):795-799. 4. Talebian Yazdi M, van Riet S, van Schadewijk A, et al. Oncotarget. 2016;7(3):3477-3488. 5. Pace E, Di Sano C, Ferraro M, et al. Eur J Cancer. 2011;47(2):296-304. 6. Speiser DE, Pittet MJ, Valmori D, et al. J Exp Med. 1999;190(6):775-782.
Clinical trial information
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Clinical trial information
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Abbreviations
ADCC
antibody-dependent cellular cytotoxicity
ALK
anaplastic lymphoma kinase
BICR
blinded independent central review
cCRT
concurrent chemoradiation therapy
DoR
duration of response
EGFR
epidermal growth factor receptor
HLA-E
HLA class I histocompatibility antigen E
HNSCC
head and neck squamous cell carcinoma
IV
intravenous
NK
natural killer
NKG2A
natural killer cell lectin-like receptor
NSCLC
non-small cell lung cancer
ORR
overall or objective response rate
OS
overall survival
PD-1
programmed cell death-1
PD-L1
programmed cell death ligand-1
PDC
platinum doublet chemotherapy
PFS
progression-free survival
PFS2
time to second progression or death
Q*W
every * weeks
Q4W
every 4 weeks
R
randomization
RECIST
Response Evaluation Criteria in Solid Tumors
TFST
time to first subsequent therapy
TTDM
time to death or distant metastases