Background: MPDL3280A (anti-PDL1) has shown activity across a number of tumor types. In FIR, we assessed the efficacy of MPDL3280A in NSCLC pts based on PD-L1 expression. Methods: FIR is a single arm study of MPDL3280A in stage IIIB/IV NSCLC. Cohort 1 included chemo-naive pts, cohort 2 included ≥ 2L pts without brain metastases and cohort 3 included ≥ 2L pts with treated asymptomatic brain metastases. Pts received 1200 mg MPDL3280A IV q3w (last pt entered Jun 27, 2014). Here, we report investigator-assessed ORR per RECIST v1.1 (data cutoff Oct 23, 2014). PD-L1 expression was centrally assayed by an SP142 IHC antibody in archival or fresh tumor biopsies (required for cohorts 2 and 3) and scored as IC 0, 1, 2 or 3 and TC 0, 1, 2 or 3. Pts with PD-L1 TC 2/3 and/or IC 2/3 tumors were enrolled. Results: Of 1,009 pts screened, 205 pts were selected based on tumor PD-L1 status. Of the 138 pts that were enrolled, 137 pts were safety-evaluable. The median age was 66 y (range, 42-85 y) and 58% of pts were male. The AE profile was similar across cohorts. Treatment-related AEs occurred in 67% of pts, most often fatigue (26%), nausea (15%) and decreased appetite (14%). Related Grade 3-4 AEs occurred in 15% of pts, with one related death due to constrictive pericarditis. 114 pts were efficacy-evaluable with ≥ 3-mo follow up in cohort 1 and ≥ 6-mo follow up in cohorts 2 and 3. The highest ORR was seen in pts with PD-L1 TC3 or IC3 tumors (Table). The median DOR has not been reached in cohorts 1 and 2 (Table). Conclusions: MPDL3280A showed clinical efficacy in both chemo-naive and previously treated NSCLC. High PD-L1 expression (TC3 or IC3) was associated with a higher ORR. The safety profile of MPDL3280A in pts with NSCLC was consistent with previous reports. (NCT01846416) Clinical trial information: NCT01846416

^aUnconfirmed ORR. ^bConfirmed ORR. 2 pts had unknown IC/TC status. ^c Median not reached.