Telisotuzumab vedotin, also known as ABBV 399 (ABBV-399; ABT 399), is a novel, first-in-class, investigational antibody-drug conjugate being developed by AbbVie comprised of the anti-c-Met antibody, ABT-700, directed against the cell surface glycoprotein mesothelia, conjugated to monomethyl auristatin E (MMAE) for the treatment of patients with solid tumors.
Although prior efforts at targeting c-Met overexpression have met with limited clinical success, an ADC directed against c-Met represents a unique strategy to deliver a potent cytotoxin directly to c-Met+ tumor cells.
ABBV-399 inhibits growth of xenograft tumors refractory to other c-Met inhibitors and provides significant therapeutic benefit in combination with standard of care chemotherapy. The investigational drug represents a novel therapeutic strategy to deliver a potent cytotoxin to c-Met-overexpressing tumor cells enabling cell killing regardless of reliance on MET signaling.[1]
ABBV-399 has progressed to a Phase I study (ongoing in the United States) where it has been well tolerated and has produced objective responses in c-Met expressing non small cell lung cancer (NSCLC) patients.
Description MOA
c-Met receptor tyrosine kinase (c-MET) (MET) (HGFR) (c-Met proto-oncogene) inhibitor.
ABT-700
The targeting moiety in telisotuzumab vedotin (ABBV-399), ABT-700, is a monoclonal antibody directed against human hepatocyte growth factor receptor (HGFR or c-Met), with potential antineoplastic activity.
Anti-c-Met monoclonal antibody ABT-700 binds to c-Met, thereby preventing c-Met binding to its ligand, HGF and the subsequent activation of the HGF/c-Met signaling pathway. This may cause cell death in c-Met-expressing tumor cells. c-Met, a receptor tyrosine kinase overexpressed or mutated in many tumor cell types, plays a key role in cancer cell growth, survival, angiogenesis, invasion, and metastasis.
Last Editorial Review: November 10, 2016
