Vebreltinib (APL-101): A Comprehensive Monograph on a Novel c-Met Inhibitor for MET-Altered Malignancies

Executive Summary

Vebreltinib is an investigational, orally bioavailable, small molecule inhibitor of the c-Met receptor tyrosine kinase, emerging as a potentially best-in-class therapeutic for cancers driven by mesenchymal-epithelial transition (MET) gene alterations. Its mechanism of action is characterized by potent, selective, and ATP-competitive inhibition of c-Met, leading to the disruption of oncogenic signaling and induction of apoptosis in tumor cells dependent on this pathway. The drug's development has been marked by a highly efficient, biomarker-driven clinical strategy, culminating in significant achievements in difficult-to-treat patient populations.

Clinically, Vebreltinib has demonstrated compelling efficacy in non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations, with the pivotal KUNPENG trial reporting an objective response rate of 75.0% and a median overall survival of 20.3 months. A key differentiating feature of Vebreltinib is its superior central nervous system (CNS) penetration, a preclinical property that has been validated by a 100% response rate in NSCLC patients with brain metastases and, most notably, a statistically significant overall survival benefit in the landmark FUGEN trial for patients with PTPRZ1−MET fusion-positive glioblastoma. This establishes Vebreltinib as a premier agent for MET-driven malignancies involving the CNS.