Xentuzumab (BI 836845)
Increased expression of
Boehringer Ingelheim is currently investigating xentuzumab, a humanised immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to and neutralises the function of human insulin-like growth factor-1 and 2 (IGF-1, IGF-2). This results in effective inhibition of IGF-induced activation of both IGF-IR and IR-A (the ‘A’ isoform of the IR).6 This IGF ligand inhibitor has shown potent
Clinical trials to evaluate xentuzumab as a treatment for patients with solid tumours7-9 including
- LeRoith D, Roberts CT, Jr. The
insulin-likegrowth factor system and cancer. Cancer Lett 2003;195(2):127-137.
- Yaktapour N, Ubelhart R, Schuler J, et al.
Insulin-likegrowth factor-1receptor (IGF1R) as a novel target in chronic lymphocytic leukemia. Blood 2013;122(9):1621-1633.
- Gallagher EJ, LeRoith D. The proliferating role of insulin and
insulin-likegrowth factors in cancer. Trends Endocrinol Metab 2010;21(10):610-618.
- Schillaci R, Galeano A,
Becu-Villalobos D,et al. Autocrine/paracrine involvement of insulin-likegrowth factor-Iand its receptor in chronic lymphocytic leukaemia. Br J Haematol 2005;130(1):58-66.
- Sachdev D, Yee D. Disrupting
insulin-likegrowth factor signaling as a potential cancer therapy. Mol Cancer Ther 2007;6(1):1-12.
- Friedbichler K, Hofmann MH, Kroez M, et al. Pharmacodynamic and antineoplastic activity of BI 836845, a fully human IGF
ligand-neutralizingantibody, and mechanistic rationale for combination with rapamycin. Mol Cancer Ther 2014;13(2):399-409.
- ClinicalTrials.gov. NCT01403974. https://clinicaltrials.gov/ct2/show/study/NCT01403974 (Accessed: November 2016).
- ClinicalTrials.gov. NCT01317420. https://clinicaltrials.gov/ct2/show/study/NCT01317420 (Accessed: November 2016).
- ClinicalTrials.gov. NCT02145741. https://clinicaltrials.gov/ct2/show/study/NCT02145741 (Accessed: November 2016).
- ClinicalTrials.gov. NCT02191891. https://clinicaltrials.gov/ct2/show/study/NCT02191891 (Accessed: November 2016).
- ClinicalTrials.gov. NCT02123823. https://clinicaltrials.gov/ct2/show/study/NCT02123823 (Accessed: November 2016).
- ClinicalTrials.gov. NCT02204072. https://clinicaltrials.gov/ct2/show/study/NCT02204072 (Accessed: November 2016).
- Lin CC, Chang KY, Huang DC, et al. A phase I dose escalation study of weekly BI 836845, a fully human, affinity-optimized, insulin-like growth factor (IGF) ligand neutralizing antibody, in patients with advanced solid cancers. J Clin Oncol 2014;32:5s, (Suppl; Abstract 2617).
- Doi T, Shitara K, Naito Y, et al. Phase I dose escalation (esc) trial of weekly intravenous (i.v.) BI 836845 in Japanese patients (pts) with advanced solid tumors. Ann Oncol 2016; 27(Suppl. 6):374P.
- Rihawi K, Ong M, Michalarea V, et al. Phase I dose escalation study of 3-weekly BI 836845, a fully human, affinity-optimized, insulin-like growth factor (IGF) ligand neutralizing antibody, in patients with advanced solid tumors. J Clin Oncol 2014;32:5s, (Suppl; Abstract 2622).
- Park K, Cho BC, Lee KH, et al. Phase Ib trial of afatinib and BI 836845 in advanced NSCLC: dose escalation and safety results. J Thorac Oncol 2017;12(Suppl.):S1187–S1188 (Abstract P3.02b-005).