Hepatocyte growth factor receptor (c-MET) and Epidermal growth factor receptor (EGFR) (c-MET/EGFR)

The target complex consists of the Hepatocyte growth factor receptor (c-MET) and the Epidermal growth factor receptor (EGFR), two prominent members of the receptor tyrosine kinase (RTK) family [UniProt, 2024]. These receptors are involved in critical cellular processes including proliferation, survival, and epithelial-to-mesenchymal transition (EMT) [National Cancer Institute, 2024]. In various malignancies, such as non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC), co-activation or crosstalk between EGFR and c-MET often drives tumor progression and mediates resistance to standard EGFR inhibitors [Merus N.V., 2024]. MCLA-129 (Petosemtamab) is a bispecific antibody designed to simultaneously target both receptors, effectively blocking their signaling pathways and inducing receptor internalization and degradation [ClinicalTrials.gov, 2024]. Additionally, it is engineered to enhance immune-mediated tumor cell killing through antibody-dependent cellular cytotoxicity (ADCC), providing a multi-pronged approach to treating cancers that rely on these pathways [Merus N.V., 2024]. By targeting both receptors, the therapy aims to overcome the bypass signaling mechanisms that frequently lead to treatment failure in patients with EGFR-mutant or MET-amplified tumors [PubMed, 2023]. This dual inhibition strategy is particularly relevant in the context of acquired resistance to first- and second-generation tyrosine kinase inhibitors [ClinicalTrials.gov, 2024].

Other names

METHGFREGFRErbB1HER1Proto-oncogene c-MetTyrosine-protein kinase MetEpidermal growth factor receptor

Dual inhibition of EGFR and c-MET signaling, receptor degradation, and induction of antibody-dependent cellular cytotoxicity (ADCC) [Merus N.V., 2024; ClinicalTrials.gov, 2024]