istiratumab   

GtoPdb Ligand ID: 8930

Synonyms: MM-141 | MM141
Compound class: Antibody
Comment: Istiratumab (MM-141) is a fully human bispecific monoclonal antibody co-targeting the IGF-I receptor (IGF-IR) and epidermal growth factor receptor ERBB3 that was developed by Merrimack Pharmaceuticals to block tumour survival signals [1,3,5].
Annotated peptide sequences for this antibody are available from its IMGT/mAb-DB record.
No information available.
Summary of Clinical Use
In November 2014, the US FDA granted Orphan Designation to MM-141 for the treatment of pancreatic cancer. Click here to link to ClinicalTrials.gov's full list of MM-141 trials. As of mid 2018 it appears that development of MM-141 has been terminated as it failed ot meet primary and secondary endpoints in Phase 2 trial in pancreatic cancer ptients.
Mechanism Of Action and Pharmacodynamic Effects
The IGF-1R and ERBB3 signaling pathways are reported to be implicated in the adoption of escape mechanisms which can develop in response to multiple targeted cancer therapies [2,4]. MM-141 treatment blocks IGF-IR and ERBB3 signaling and prevents cells from adapting to use redundant PI3K/AKT/mTOR survival pathways [3] which can result in enabling downstream resistance mechanisms.