Background: Approximately 10% of EGFR mutants harbor uncommon mutations, which represent a heterogeneous group of rare molecular alterations within exons 18-21 and the sensitivity to EGFR TKIs is variable. Osimertinib is a potent irreversible inhibitor of both sensitizing EGFR mutation and T790M. In preclinical data, the potency of osimertinib against uncommon EGFR mutants other than exon 20 insertion was fairly good. Here we present the efficacy and safety of osimertinib in patients with uncommon EGFR mutation positive NSCLC. Methods: Patients with histologically confirmed metastatic or recurrent NSCLC with activating EGFR mutation other than exon 19 deletion, L858R, T790M and insertion in exon 20 were eligible. Patients received 80mg of osimertinib per oral daily until progression or unacceptable toxicity. Response was assessed every 8 weeks by investigator. The trial was registered with ClinicalTrials.gov, number NCT03424759. Results: Between Mar 2016 and Oct 2017, 36 patients were enrolled. Median age was 59.5, 61% male, 44% never smoker, 97% adenocarcinoma. 61% of patients were treated as first-line therapy. The most common mutations are G719A/C/D/S/X (19, 52.8%) followed by L861Q (9, 25%), S7681 (8, 22%), and others (4, 11%). The overall response rate was 50.0% (95% CI 32.8-67.2) and DCR was 88.9% (95% CI 78.1-99.7). Seven patients (77.8%) with L861Q mutation achieved partial response; 10 (52.6%) with G719A/C/D/S/X mutation; three (37.5%) with S768I mutation. At data cutoff (Nov, 2017), the median PFS was 9.5 months (range 1.0-20.1) and median duration of response was 7.0 months (95% CI 4.7-9.3). The most common adverse events were rash (n = 11, 30.6%), anorexia (n = 8, 22.2%), and diarrhea (n = 7, 19.4%). Grade 3 or 4 AEs were reported in 8 of 36 patients (22%), but all of AEs were manageable. Conclusions: Osimertinib showed highly active and durable in NSCLC patients harboring uncommon EGFR mutation with manageable safety profile, consistent with previous reports. Further analysis will be updated. Clinical trial information: NCT03424759