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BI 836880: A dual inhibitor of two key pathways mediating tumour angiogenesis
BI 836880* is a humanised bispecific nanobody® comprising blocking domains for vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2) and an additional portion for extending the half-life.1 BI 836880 potently and selectively inhibits VEGF and Ang2.1 BI 836880 is currently being investigated as monotherapy in two Phase I clinical studies in patients with solid tumours.2,3 BI 836880 is also being investigated in combination with the programmed cell death protein-1 (PD-1) inhibitor BI 754091* in a Phase I clinical study in patients with advanced non-squamous non-small cell lung cancer (NSCLC).4
The role of VEGF/Ang2 signalling
Signalling via VEGF and via Ang2 has different but complementary functions in tumour angiogenesis.5,6 Crosstalk between the signalling pathways via VEGFR2 and Tie2 suggests that dual inhibition may control tumour growth better than blocking either individual pathway alone.6
Ang2 interrupts signalling via Tie2, allowing the destabilisation of established blood vessels. This promotes remodelling and is a prerequisite for sprouting angiogenesis.6,7
Signalling via VEGF regulates endothelial cell proliferation and migration, and vessel sprouting.6,7
Dual blockade of signalling via VEGF and Ang2 has been shown to increase survival compared with blockade of either pathway alone in mouse models of various solid tumours.5
About BI 836880
BI 836880’s mechanism of action
BI 836880 is a humanised bispecific nanobody® (antibody fragments consisting of a single variable antibody domain) comprising blocking domains for VEGF and Ang2 and an additional portion for extending the half-life.1 BI 836880 potently and selectively inhibits VEGF and Ang2.1
Preclinical and clinical development: solid tumours
BI 836880 has shown promising in vitro and in vivo activity in oncology.1 Preclinical data have shown that BI 836880 can potently and selectively neutralise VEGF and Ang2 in models of pancreatic, lung, renal, ovarian and colon cancer.1 When compared with bevacizumab, a VEGF inhibitor, and AMG 368, an Ang1/2 inhibitor, BI 836880 showed superior tumour growth inhibition and inhibition of angiogenesis in vivo.1
BI 836880 is currently being investigated in three Phase I clinical trials. Two trials are investigating BI 836880 as a monotherapy in patients with solid tumours.2,3 A third trial is investigating BI 836880 in combination with the PD-1 inhibitor BI754091 in patients with advanced non-squamous NSCLC.4
AE, adverse event; Ang2, angiopoietin 2; DLT, dose-limiting toxicity; DoR, duration of response; MTD, maximum tolerated dose; OR, objective response; PD, pharmacodynamics; PD-1, programmed cell death protein-1; PFS, progression free survival; PK, pharmacokinetics; VEGF, vascular endothelial growth factor.
Hofmann I, et al. Poster presentation at the 8th Euro Global Summit on Cancer Therapy 2015.
ClinicalTrials.gov. NCT02674152. http://clinicaltrials.gov/ct2/show/NCT02674152 (Accessed: September 2018).
ClinicalTrials.gov. NCT02689505. http://clinicaltrials.gov/ct2/show/NCT02689505 (Accessed:September 2018).
ClinicalTrials.gov. NCT03468426. https://clinicaltrials.gov/ct2/show/NCT03468426 (Accesssed: September 2018).
Fukumura D, et al. Nat Rev Clin Oncol 2018;15(5):325–40.
Gerald D, et al. Cancer Res 2013;73(6):1649–57.
Huang H, et al. Nat Rev Cancer 2010;10(8):575–85.
*This is an investigational compound and has not been approved. Its safety and efficacy have not been established.
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Last updated: November 2018
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