Click here for international medical scientific information about Oncology for Healthcare Professionals.
Click here for general international information for patients, caregivers and the general public.
BI 754111: A lymphocyte-activation gene 3 targeting monoclonal antibody
BI 754111* is a humanised lymphocyte-activation gene 3 (LAG-3) targeting monoclonal antibody (mAb) that inhibits the interaction between LAG-3 and its ligand major histocompatibility complex (MHC) Class II.1 This reduces immune cell exhaustion, allowing T cells to continue to destroy tumour cells.2 BI 754111 is currently being investigated in combination with the programmed death-1 (PD-1)-targeting mAb BI 754091* in Phase I trials in solid tumours.3,4
The role of LAG-3
LAG-3 is an immune checkpoint receptor located on the surface of T cells in the tumour microenvironment.5
MHC Class II molecules on the surface of tumours present antigens that are recognised by T-cell receptors, initiating a signalling pathway that promotes an adaptive immune response to the tumour.5
In the presence of antigens, LAG-3 binds to the MHC Class II molecule on the tumour cell, starting a signalling cascade that reduces T-cell activation and proliferation.5
Preclinical studies suggest that the expression of LAG-3 on T cells and binding to its ligand MHC II within the tumour microenvironment contributes to immune cell exhaustion, a state in which T cells can no longer proliferate in response to antigen presentation, and lack cytotoxic activity.2,5,6 Immune cell exhaustion is thought to be a tumour cell escape mechanism, allowing them to avoid immune detection and destruction.2
Exhausted T cells expressing LAG-3 are known to be present at tumour sites.5,7 Preclinical studies suggest that LAG-3 inhibition allows T cells to regain their cytotoxic function and inhibit tumour growth.8
About BI 754111
Mechanism of action
BI 754111 is a humanised LAG-3-targeting mAb that inhibits the interaction between LAG-3 and its ligand, MHC II.1 LAG-3 inhibition may be able to reduce the effects of T-cell exhaustion, such as impaired immune cell proliferation and cytokine production, and restore the immune response to the tumour cell.2,4,9
Preclinical studies have demonstrated that the sustained co-expression of LAG-3 and PD-1 on tumour-invading CD4 and CD8 T cells dampens the immune response to tumour cells.2 Rationally designed synergistic combination therapies, such as the dual blockade of PD-1 and LAG-3, should enhance anti-tumour activity compared with immune checkpoint inhibitor monotherapy.1,2
BI 754111 is currently being investigated in combination with the PD-1 inhibitor BI 754091 in two Phase I studies in solid tumours.3,4
DLT, dose-limiting toxicity; DoR, duration of response; LAG-3, lymphocyte-activation gene 3; MTD, maximum tolerated dose; OR, objective response; PD-1, programmed cell death protein-1; PFS, progression-free survival; PK, pharmacokinetics; PK/PD, pharmacokinetics/pharmacodynamics.
Zettl M, et al. Annual Meeting of the American Association for Cancer Research 2018; Abstract 4547.
Andrews LP, et al. Immunol Rev 2017;276(1):80–96.
ClinicalTrials.gov. NCT03156114. https://clinicaltrials.gov/ct2/show/NCT03156114 (Accessed: August 2018).
ClinicalTrials.gov. NCT03433898. https://clinicaltrials.gov/ct2/show/NCT03433898 (Accessed: August 2018).
Turnis ME, et al. Eur J Immunol 2015;45(7):1892–905.
Maçon-Lemaître L, Triebel F. Immunology 2005;115(2):170–8.
Huang CT, et al. Immunity 2004;21(4):503–13.
Camisaschi C, et al. J Immunol 2010;184(11):6545–51.
Grosso JF, et al. J Clin Invest 2007;117(11):3383–92.
*This is an investigational compound and has not been approved. Its safety and efficacy have not been established.
© 2018 Boehringer Ingelheim International GmbH. All rights reserved.
Last updated: October 2018
Using this link will let you leave a website of Boehringer Ingelheim International GmbH (“BI”) or to a different domain under the control of BI. In the event that the linked site is not under the control of BI but under the control of a third party or an affiliate in the Boehringer Ingelheim group of companies, BI shall not be responsible for the contents, processing of personal data of any linked site or any link contained in a linked site, or any changes or updates to such sites. This link is provided to you only as a convenience, and the inclusion of any link does not imply endorsement by BI of the site.
Do you want to continue ?Continue