Sym015 has a strong scientific rationale and constitutes an attractive niche indication opportunity with a possible orphan drug development path. Sym015 is well tolerated with an excellent safety profile and we remain encouraged by the clinical results to date.
Sym015 has the potential to treat patients with solid tumors showing alterations and/or amplification of the MET proto-oncogene including certain lung cancers.
METexon14 alterations are detected in approximately 3–4% of lung adenocarcinomas. The prevalence of MET-amplification in NSCLC ranges from 1% to 5%. Although MET-amplification occurs in a relatively small percentage of patients, it is present in several highly prevalent cancers including NSCLC, gastric cancer, mCRC and renal cell carcinoma. Based on an administrative interim analysis of safety and efficacy, we have decided to focus on lung cancer patients.
Mechanism of action
The two mAbs of Sym015 bind to non-overlapping epitopes on the SEMA-a domain of MET. This allows the antibodies to bind simultaneously to the receptor and effectively induce receptor internalization and degradation. Through this mechanism, Sym015 inhibits tumor cell growth and proliferation in vitro and tumor growth in vivo, in models where MET is constitutively activated. Sym015 blocks binding of the ligand HGF to the receptor and thereby inhibits ligand-induced MET activation.
PMID: 28679766 [PubMed - as supplied by publisher]