Objectives: Non-Small Cell Lung Carcinomas (NSCLC) presents mesenchymal-epithelial transition factor exon 14 skipping (METex14) mutation in 0.6-7 % of patients. Crizotinib is a Tyrosine Kinase Inhibitor (TKI) that has been approved for the treatment of ALK-rearranged tumors and demonstrated clinical activity in MET(+) NSCLC. Acquired point mutations in the MET gene have been described as mechanisms of resistance to crizotinib. 
 
Materials and Methods: For the evaluation of the MET clones we have used cell-free DNA (cfDNA) NGS test (Guardant360). 
 
Results: In this report, we present a 66-year-old previously healthy non-smoking male who was diagnosed with metastatic adenocarcinoma of the lung with METex14 mutation, PDL-1 expression more than 50 %. The patient developed multiple secondary c-MET resistant clones and responded to re-exposure to crizotinib therapy. 
 
Conclusion: According to this case we suggest that clonal evolution is not necessarily a synonymous with resistant to previous lines (beyond the recent one). Similar phenomenon was previously reported in an ALK fusion case with respond to crizotinib re-exposure, by Shaw et al. The eradication of the emerging clones by crizotinib, as presented in this case, may support this assumption and suggest cautious re-exposure to previous lines in case of emerging resistant. Hypothetically, if this is not the case, we may suggest that crizotinib has changed the microenvironment in a way allowing eradication of the different clones by the activated immune system, however we do not have any support for this assumption. 

Keywords: Targeted therapy; Non-small cell lung carcinoma (NSCLC); c-MET Acquired resistance; Crizotinib