Telisotuzumab vedotin (Teliso-V; ABBV-399) is a c-Met-targeted antibody-drug conjugate (ADC) comprised of the ABT-700 (c-Met-targeting) antibody conjugated to the cytotoxic microtubule inhibitor monomethylauristatin E (MMAE) via a cleavable valine–citrulline (vc) linker.
Proposed Mechanism of Action
The c-Met receptor tyrosine kinase is the cell surface receptor for hepatocyte growth factor (HGF) encoded by the MET protooncogene. MET is aberrantly activated in cancers contributing to tumor progression, angiogenesis, invasiveness, metastasis, and resistance and is overexpressed in non-small cell lung cancer (NSCLC; 40%) and several other solid tumor types.1
Prior c-Met inhibitors require MET amplification and/or c-Met activation for activity; however, as demonstrated in preclinical models, Teliso-V uses c-Met to deliver a cytotoxin to c-Met-overexpressing tumor cells enabling cell killing regardless of reliance on MET signaling.1 Although, MET amplification is a therapeutically actionable target, it generally occurs in 1% to 5% of de novo cancers, whereas c-Met overexpression is more common, occurring in up to 50% of many advanced solid tumors.2
The use of an ADC that targets c-Met–positive tumors represents a therapeutic strategy with which to induce tumor cell killing independently of MET signaling pathway inhibition because it involves the delivery of the potent cytotoxin MMAE directly to c-Met–positive tumor cells.2
Although a c-Met–targeting ADC may present the risk of on target toxicity based on c-Met normal tissue expression, preclinical and early phase results have demonstrated a strong correlation between Teliso-V anti-tumor activity and c-Met expression levels as c-Met expression is significantly higher in many cancers compared with normal tissue.1
Teliso-V is in phase 3 development in patients with previously treated c-Met+ non-small cell lung cancer (NSCLC).
View select clinical trials with telisotuzumab vedotin now. To view a full list of clinical trials in which telisotuzumab vedotin is being investigated, please visit ClinicalTrials.gov.
Telisotuzumab vedotin is an unapproved investigational drug under clinical development. Safety and efficacy have not been established.
- Wang J, Anderson MG, Oleksijew A, et al. ABBV-399, a c-Met antibody-drug conjugate that targets both MET-amplified and c-Met-overexpressing tumors, irrespective of MET pathway dependence. Clin Cancer Res. 2017 Feb 15;23(4):992-1000.
- Strickler JH, et al. First-in-Human Phase I, Dose-Escalation and -Expansion Study of Telisotuzumab Vedotin, an Antibody–Drug Conjugate Targeting c-Met, in Patients With Advanced Solid Tumors. Journal of Clinical Oncology . 2018;36(33):3298-3306.
c-Met+ Non Small Cell Lung Cancer (NSCLC)