TRAILR2/CDH17 antibody (BI 905711)

TRAILR2/CDH17 antibody (BI 905711)

TRAILR2/CDH17 antibody (BI 905711)

BI 905711: a TRAILR2/CDH17 antibody

BI 905711* is a tetravalent bispecific antibody that cross-links the pro-apoptotic tumor necrosis factor (TNF)-related apoptosis-inducing ligand receptor 2 (TRAILR2) with the tumor cell anchor cadherin 17 (CDH17). CDH17-dependent clustering of TRAILR2 allows BI 905711 to induce selective apoptosis in CDH17-expressing tumor cells.1

 

Clinical trials: BI 905711 is currently being investigated in patients with advanced gastrointestinal (GI) cancers.2

Role of TRAILR2 and CDH17

TRAILR2 is a pro-apoptotic receptor that is widely expressed in normal tissues and in many types of tumors.3,4 Receptor clustering is required for activation of the extrinsic apoptotic pathway.5

CDH17 is a cell-adhesion protein that is broadly expressed on GI tumor cells. It was selected as the anchor target for BI 905711 owing to its limited expression in liver tissue, which may help to avoid clinical hepatotoxicity that can be associated with TRAILR2 agonism.

About BI 905711

Mechanism of action

BI 905711 is a tetravalent bispecific antibody that cross-links TRAILR2 with CDH17. The antibody cross-linking induces CDH17-dependent clustering (oligomerization) of TRAILR2, leading to the activation of the apoptotic pathway and killing of CDH17-expressing tumor cells.1

The use of CDH17 as the anchor protein means that BI 905711 is a targeted treatment strategy for CDH17-positive tumors, such as many colorectal cancers (CRC).1

Mechanism of action: tumor cell apoptosis1

BI TRAILR2/CDH17 antibody mechanism of action
CDH, cadherin; TRAILR2, tumor necrosis factor-related apoptosis-inducing ligand receptor 2.

Watch the TRAILR2/CDH17 antibody mechanism of action animation

Watch the TRAILR2/CDH17 antibody mechanism of action animation

Preclinical development

BI 905711 has shown significant inhibition of tumor growth in patient-derived xenograft models of CRC. Tumor regression was sustained for up to approximately 30 days. Decrease in tumor size was accompanied by modulation of apoptosis markers with good correlation between tumor and plasma biomarker modulation.1

More information about Boehringer Ingelheim oncology clinical trials can be found on the MyStudyWindow website. Relevant trials for the TRAILR2/CDH17 antibody include: BI 1412-0001

Clinical development

BI 905711 is currently being investigated as a monotherapy in patients with advanced GI cancers.

TRAILR2/CDH17 antibody (BI 905711) clinical trial

TRAILR2, tumor necrosis factor-related apoptosis-inducing ligand receptor 2.
Trial number Phase Treatment Patient population Status

NCT041372892 (1412.1)

Ia/b

TRAILR2/CDH17 antibody monotherapy

Patients with advanced, unresectable or metastatic gastrointestinal cancers

Recruiting

Explore our latest TRAILR2/CDH17 antibody data

Our latest data on the clinical trial program for the TRAILR2/CDH17 antibody (BI 905711) were presented at the ESMO World Congress on Gastrointestinal Cancer (ESMO WCGC) 2020.

Did you find this information useful?

References

1

Garcia-Martinez JM, et al. American Association for Cancer Research Annual Meeting 2019; Abstract 2051.

2

ClinicalTrials.gov. NCT04137289. https://clinicaltrials.gov/ct2/show/NCT04137289 (Accessed: February 2021).

3

Ashkenazi A, Dixit VM. Science 1998;281:1305–8.

4

Ashkenazi A, et al. J Clin Invest 1999;104(2):155–62.

5

Naval J, et al. Cancers (Basel) 2019;11(4):pii: E444.

*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.

 

Last updated: March 2021