Background: Alflutinib (AST2818) is a third generation EGFR-TKI. This phase IIb, multicenter, single arm study (ALSC003, NCT03452592) aimed to assess the efficacyand safety of Alflutinib in patients with EGFR T790M mutated non-small cell lung cancer (NSCLC). Methods: Patients with locally advanced or metastatic EGFR T790M mutated NSCLC who progressed after first/second-generation EGFR-TKIs therapy or primary EGFR T790M mutation positive received 80 mg Alflutinib orally once daily. Tumor tissue samples underwent central laboratory testing for EGFR T790M mutation. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. Efficacy was assessed by independent radiological review committee per RECIST 1.1. Safety was assessed by NCI CTCAE version 4.03. Results: From Jun 4, 2018 to Dec 8, 2018, 220 patients were enrolled with a median age of 61.0 (range 29 to 80) years. According to the AJCC version 8 staging system, 212 (96.4%) cases were in stage IV, and 8 (3.6%) cases in stage III. All patients had EGFR T790M mutation. By April 12, 2019, the ORR was 73.6% (95% CI 67.3–79.3). The DCR estimated at 6 and 12 weeks were 87.3% (95%CI 82.1-91.4) and 82.3% (95%CI 76.6-87.1), respectively. The median PFS was 7.6 months (95% CI 7.0–NA). Median OS and DoR have not been reached. 209 (95.0%) patients had at least one adverse events (AEs), which were mostly grade 1 or 2 and well tolerable. The most common AEs were increased aspartate aminotransferase (33 [15.0%]), upper respiratory tract infection (33 [15.0%]), and cough (33 [15.0%]). Grade 3 to 5 AEs occurred in 42 (19.1%) patients. The most common one was elevated γ-glutamyltransferase (n = 4). There were 3 deaths patients, 2 of which possibly not be related to the study drug, and 1 could not be determined. No interstitial pneumonia was reported. Conclusions: Alflutinib has promising efficacy and acceptable safety profile for the treatment of EGFR T790M mutated NSCLC patients. Clinical trial information: NCT 03452592.