DLL3-CD3 T-cell engager

DLL3/CD3 bispecific antibody

DLL3/CD3 T-cell engager

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

Clinical trials (monotherapy): our DLL3/CD3 T-cell engager is being investigated in patients with small cell lung cancer (SCLC) and other neuroendocrine tumors (NETs) that are positive for DLL3.3

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, but not in normal adult 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 our DLL3/CD3 T-cell engager

Mechanism of action

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

The pharmacological effect of the DLL3/CD3 T-cell engager 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 T-cell engager in a range of DLL3-positive tumor models.2

T-cell engager mechanism of action1

DLL3/CD3 T-cell Engager MoA
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 T-cell engager 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 T-cell engager with PD-1 inhibitors (such as ezabenlimab) in order to revert this upregulation.1,2

Clinical development

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

DLL3/CD3 T-cell engager 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 T-cell engager

Advanced SCLC and other NETs expressing DLL3

Recruiting

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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: September 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: September 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.

 

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Page last updated: September 2021