Background: Platinum-based chemotherapy, before or after surgery, provides only a 5% benefit in 5yr. OS in locally advanced NSCLC. A recent pilot study (JCO 2017 35:15suppl, 8508) showed that preoperative immune checkpoint inhibitor therapy was well tolerated and yielded a clinically meaningful major pathologic response rate (MPR ≤10% residual viable tumor cells). This large multicenter trial tests the MPR rate and novel biomarkers of benefit using this novel neoadjuvant approach with atezolizumab (atezo) [NCT02927301]. Methods: Pts with stages IB -selected IIIB resectable NSCLC were to receive 2 cycles of atezo (1200 mg, days 1, 22) then undergo resection (day 40 +/- 10). Chest CT, PET obtained pre- and post atezo to assess clinical response. Primary tumor +/- node biopsies and blood samples were obtained before atezo and at surgery for biomarker studies. The primary endpoint was MPR. Secondary endpoints included safety, response by PD-L1, OS, and DFS. Results: For the prespecified initial safety analysis, the first 21 of 180 planned pts (67 pts currently on study) are reported: 13 males, median age 65 y, all ECOG 0-1; 4 current, 16 former smokers; 13 non-squamous NSCLC; clinical stages Ib/IIa/IIb/IIIa/IIIb = 4/2/6/5/4. Two pts received one dose of atezo due to treatment related AE (Gr 1 pyrexia, Gr 2 dyspnea) but underwent uncomplicated resection with MPR assessment. There were no Gr 5 AE, 5 Gr 3-4 AE (1 treatment related). By RECIST, 20 pts had SD, and 1 had PD. There were no major delays to surgery. 19 pts had MPR assessment: 1 pt discontinued atezo preop due to CNS mets and 1 pt had unresectable disease. MPR rate was 4/19 (21%, 95% CI 6-46). Excluding 2 pts who had known driver mutations (1 EGFR+, 1 ALK+), MPR rate was 4/17 (24%, 95% CI 7-50). 11/19 patients had ≤50% viable tumor. Conclusions: This first report of atezo in the neoadjuvant setting shows that preoperative treatment is feasible and well tolerated. MPR rate is encouraging. Clinical and pathological responses are often discordant. Safety and efficacy results from additional pts will be presented. Correlative analyses on pre- and post atezo tissues are ongoing. Preliminary correlative analyses in blood samples are included in a separate abstract. Clinical trial information: NCT02927301