DLL3/CD3 bispecific antibody

DLL3/CD3 bispecific antibody

DLL3/CD3 bispecific antibody

Our delta-like canonical Notch ligand 3/cluster of differentiation 3 (DLL3/CD3) bispecific antibody* functions as a T-cell engager, acting as a bridge that selectively directs the activity of cytolytic T cells to DLL3-expressing tumor cells.1,2

Clinical trials (monotherapy): our DLL3/CD3 bispecific antibody is being investigated in patients with small cell lung cancer (SCLC) and other neuroendocrine tumors (NETs).3

Role of DLL3

DLL3 is an inhibitory Notch ligand that is expressed in tumors with a neuroendocrine origin, such as small-cell lung cancer (SCLC), glioblastoma multiforme, carcinoids and pediatric tumors – with no to minimal expression in normal tissue.4-6 Notch pathway signaling is involved in a variety of development processes, including the development of pulmonary neuroendocrine cells.5 DLL3 expression inhibits Notch signaling, which is downregulated during neuroendocrine tumor growth.5

About DLL3/CD3 bispecific antibody

Mechanism of action

Our DLL3/CD3 bispecific antibody acts as a T-cell engager with an extended half-life.1 The DLL3/CD3 bispecific antibody selectively directs the activity of cytolytic T cells to DLL3-expressing tumor cells.1,2

The pharmacological effect of the DLL3/CD3 bispecific antibody depends on its ability to bind simultaneously to CD3 on T cells and to DLL3 expressed on tumor cells, resulting in the formation of a cytolytic synapse.1,2

Preclinical studies have demonstrated the antitumor activity of the DLL3/CD3 bispecific antibody in a DLL3-positive tumor model of SCLC.2

T-cell engager mechanism of action1

T-cell engager mechanism of action
CD3, cluster of differentiation 3; DLL3, delta-like canonical Notch ligand 3.

Watch the T-cell engager mechanism of action animation

Watch the T-cell engager mechanism of action animation

Combination therapy

The binding of the DLL3/CD3 bispecific antibody to CD3 may lead to programmed cell death protein 1 (PD-1) upregulation in activated T cells and programmed death-ligand 1 upregulation on malignant cells.2 Preclinical evidence supports the combination of the DLL3/CD3 bispecific antibody with PD-1 inhibitors (such as ezabenlimab) in order to revert this upregulation.1,2

Clinical development

Our DLL3/CD3 bispecific antibody is currently being investigated as a monotherapy in patients with SCLC and NETs in an ongoing Phase Ia study.3

DLL3/CD3 bispecific antibody clinical trial

CD3, cluster of differentiation 3; DLL3, delta-like canonical Notch ligand 3; NET, neuroendocrine tumor; SCLC, small-cell lung cancer.
Trial number Phase Treatment Patient population Status

NCT04429087(1438.1)

Ia

DLL3/CD3 bispecific antibody

SCLC and other NETs

Recruiting

Did you find this information useful?

References

1

Boehringer Ingelheim. Data on file.

2

Hipp S, et al. Cancer Res 2019;79(13 Suppl.): Abstract 549.

3

ClinicalTrials.gov. NCT04429087. http://clinicaltrials.gov/ct2/show/NCT04429087 (Accessed: February 2021).

4

National Center for Biotechnology Information. DLL3 delta like canonical Notch ligand 3 [Homo sapiens (human)]. https://www.ncbi.nlm.nih.gov/gene/10683 (Accessed: February 2021).

5

Owen DH, et al. J Hematol Oncol 2019;12(1):61.

6

Saunders LR, et al. Sci Transl Med 2015;7(302):302ra136.

*This is an investigational compound and has not been approved. Its safety and efficacy have not been established.

 

© 2021 Boehringer Ingelheim International GmbH. All rights reserved.

 

Page last updated: March 2021