AbbVie Submits BLA for Telisotuzumab Vedotin, the First-in-Class c-Met ADC to Reach Phase III

Source: PharmaCube Info

Recently, the U.S. ClinicalTrials registry (ClinicalTrials.gov) indicates that AbbVie's c-Met-targeting antibody-drug conjugate (ADC) telisotuzumab vedotin has registered a Phase III clinical trial, marking it as the first c-Met ADC globally to enter Phase III clinical development.

ClinicalTrials.gov

PharmCube NextPharma

This study is an open-label, randomized, controlled, global Phase III clinical trial designed to compare the efficacy and safety of telisotuzumab vedotin (ABBV-399) versus docetaxel in previously treated patients with c-Met-positive, EGFR wild-type, locally advanced/metastatic non-squamous non-small cell lung cancer. The study will enroll 600 subjects across 250 centers globally. Subjects will receive telisotuzumab vedotin via intravenous infusion every 2 weeks or docetaxel via intravenous infusion every 3 weeks until criteria for discontinuation of the investigational product are met. The trial is expected to commence on December 10, 2021, and conclude on March 9, 2027.

US Clinical Trials Network

The receptor tyrosine kinase MET gene, formally known as the mesenchymal-epithelial transition factor (MET), is also referred to as cellular mesenchymal-epithelial transition factor (c-Met) or hepatocyte growth factor receptor (HGFR). Extensive research indicates that the overactivation of c-Met may initiate the transformation of normal cells into tumor cells, subsequently driving downstream events such as invasion, metastasis, and dissemination.

Upon binding to its ligand HGF (hepatocyte growth factor), c-Met undergoes dimerization and autophosphorylation, activating a series of downstream signaling pathways that initiate associated cellular physiological and biochemical functions. Many of the molecules involved in the c-Met signaling pathway are prominent targets in oncology drug development, such as PI3K, GRB2, STAT3, GAB1, SHP2, and RAS. The activation of these targets often triggers their own associated, more complex and extensive regulatory networks. Recent clinical findings also indicate that c-Met gene mutations are a critical factor underlying resistance to many oncology drugs.

Schematic Diagram of c-Met-Related Signaling Pathways

Telisotuzumab vedotin (ABBV-399) is a first-in-class ADC developed by AbbVie, consisting of a humanized anti-c-Met monoclonal antibody (ABT-700) conjugated to the cytotoxin monomethyl auristatin E (MMAE) via a valine-citrulline linker (ABT-700 vcMMAE).

Currently, there are four c-Met ADCs in clinical development globally. In addition to AbbVie’s telisotuzumab vedotin, they include RemeGen’s RC108 (Phase I), Hengrui Pharmaceuticals’ SHR-A1403 (Phase I), and Concortis Biosystems’ c-Met-0174 (Phase I).

Note: The original text has been abridged.