A 66-yr-old woman without significant comorbidities was diagnosed with metastatic adenocarcinoma of the right lung...Subsequent RNA next-generation sequencing (NGS) of the tumor identified transcripts of KLC1 exon 9 fused with ALK exon 20 (K9–A20)...Second-line treatment with crizotinib (250 bid) was initiated...During the next disease progression with multiple new brain lesions 50 d later...four distinct secondary mutations in the kinase domain of the ALK gene were identified in ctDNA...