CAPZA2::MET Fusion and MET Amplification in EGFR-Mutated Advanced Non–Small Cell Lung Cancer With Marked Response to Capmatinib Monotherapy: A Case Report

CAPZA2::MET fusion is an exceptionally rare MET rearrangement in non–small cell lung cancer (NSCLC), and clinical evidence supporting MET-targeted therapy is limited. We report a 62-year-old woman with metastatic EGFR L858R-mutated lung adenocarcinoma in whom CAPZA2::MET fusion and MET amplification were detected after progression on osimertinib, amivantamab–carboplatin–pemetrexed, and atezolizumab–bevacizumab–carboplatin–paclitaxel. EGFR L858R was not detected in the progressing lung lesion. Capmatinib monotherapy produced rapid clinical improvement, recovery of performance status, and a confirmed partial response. At progression after 5 months, CAPZA2::MET was not detected in the repeat lung biopsy, whereas MET copy-number status was not evaluable. This case illustrates capmatinib activity in a tumor harboring concurrent CAPZA2::MET fusion and MET amplification, the dynamic nature of tumor heterogeneity, and the importance of repeat molecular testing at disease progression.