The Landscape of Clinical Trials for Targeting c-MET Therapy

Mesenchymal-epithelial transition factor (c-MET) is a pivotal receptor tyrosine kinase that mediates tumor initiation, progression and metastasis through abnormal signaling activation, representing a promising therapeutic target across malignancies. This study systematically summarizes the global landscape of c-MET-targeted clinical trials to inform future drug development and clinical practice. On the basis of rigorous screening of multiple international clinical trial databases, 1,389 eligible trials were included and analyzed in terms of phase, distribution, indications, and therapeutic agents. Overall, c-MET-targeted clinical research is expanding rapidly, dominated by early-phase trials (phase I/II, 70.12%), with a notable increase since 2017. Geographically, trials are concentrated in North America, Asia and Europe, with the United States and China as the major contributors and key collaborative hubs. Non-small cell lung cancer is the most extensively studied indication, followed by unspecified solid tumors. Tyrosine kinase inhibitors, particularly cabozantinib, remain the most investigated agents, while antibody-drug conjugates, immune checkpoint inhibitors and combination strategies have emerged as major research focuses. Recent advances reported at the 2025 ASCO meeting highlight encouraging activity of novel c-MET-targeted ADCs in lung and gastrointestinal cancers, as well as promising potential of tetra-specific T-cell engagers. Collectively, c-MET is a core target in oncology, with rapidly evolving therapeutic agents and strategies. The development of innovative drugs and rational combinations will continue to refine c-MET-targeted therapy and expand treatment options for patients with c-MET-aberrant tumors.