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Purpose: Osimertinib, a third-generation irreversible mutant-selective inhibitor of EGFR kinase activity was clinically evaluated in the AURA trials, where it showed high clinical efficacy and a favorable toxicity profile in patients with acquired exon 20-EGFR pT790M mutation. We provide the clinical data of the German expanded access program that further characterizes the efficacy and safety of osimertinib in a heterogeneous patient population outside clinical trials., Methods: We performed a retrospective data analysis on patients who were included into the German osimertinib EAP., Results: Of 81 patients enrolled, 51 patients (62.9%) with sufficient case report form data were available for efficacy and safety analysis. Unconfirmed overall response rate was 80.0% with 2 patients (3.9%) achieving a complete remission and 37 patients (72.5%) having a partial remission. Disease control rate was 95.9% and only two patients showed refractory disease. Disease control rate did not correlate with clinical characteristics and was independent of number as well as type of the previous therapy line(s). Estimated progression-free survival was 10.1 months (95% CI 9.2-11.0 months). Osimertinib showed a favorable toxicity profile with no dose reductions in our observation period, even in patients with low performance status. Median survival from first diagnosis to data cut-off was 47.3 months (95% CI 43.3-51.9 months). Repeated tissue/liquid biopsy of three patients in our cohort who showed disease progression revealed an amplification of MET., Conclusions: We confirm safety and efficacy of osimertinib with high response rates among all subgroups, including patients with poor performance status and multiple prior therapy lines. Amplification of MET might mediate acquired resistance to osimertinib.