Alterations in c-MET, a tyrosine kinase receptor encoded by the MET gene, have 
been reported in approximately 3% of non-small cell lung cancer (NSCLC) cases 
and carry important treatment implications. The best studied genetic alterations 
are exon 14 skipping and gene amplification; however, gene rearrangement has 
also been described, and multiple fusion partners have been reported. Recently, 
in METex14-mutated NSCLC, multitarget tyrosine kinase inhibitors (TKIs), such as 
crizotinib and cabozantinib, as well as MET-selective TKIs, such as tepotinib 
and capmatinib, have demonstrated durable responses. In this study, we present 
the case of a 41-year-old woman with advanced NSCLC harboring an HLA-DRB1-MET 
gene fusion. The patient was offered successively two different MET multikinase 
inhibitors, crizotinib and cabozantinib, and the selective inhibitor tepotinib. 
Each time, including under tepotinib, the patient experienced rapid and complete 
responses associated with a tremendous improvement in her physical function. KEY 
POINTS: To our knowledge, this is the first report of a patient with non-small 
cell lung cancer harboring an HLA-DRB1-MET gene fusion demonstrating a clinical 
response to multiple MET inhibitors, including tepotinib. This finding 
illustrates the efficacy and rationale to targeting MET regardless of fusion 
partner and gives insight to pooling of patients with different MET fusion 
products in trials assessing safety and efficacy of novel molecules.