ABSTRACT Aim: PD-L1, which can mediate cancer immune evasion, is broadly expressed in RCC. As RCC can respond to immune-based therapy, blocking PD-L1 represents a strategy to restore tumor-specific T-cell immunity. MPDL3280A, a human mAb containing an engineered Fc-domain, targets PD-L1 to prevent binding to its receptors PD-1 and B7.1 on activated T cells. Interim results showed that MPDL3280A had a manageable safety profile and clinical activity in advanced NSCLC, melanoma and mRCC pts. Here, we report long term follow up and correlative data for the RCC cohort. Methods: mRCC pts were enrolled in a Ph I expansion study. All pts who received MPDL3280A IV q3w at doses of 3-20 mg/kg were evaluable for safety. Pts were treated for ≤ 1 y. Response was assessed by RECIST v1.1. PD-L1 IHC was centrally assessed in tumor biopsies. Results: As of Jan 1, 2014, among 69 mRCC pts evaluable for safety, median age was 61 y and all were ECOG PS 0-1 (48% PS 1). 94% of pts had prior nephrectomy and 87% received prior systemic therapy, including cytokines (39%), VEGF-inhibition (64%) and mTOR inhibitors (26%). Pts received MPDL3280A for a median duration of 7.7 m (0.7-24.3 m). 80% of pts had a treatment-related AE; however, the frequency of G3 related events was 16%, including anemia, dehydration, fatigue and hypophosphatemia (3% each). No related G4 AEs or deaths occurred. Clinical activity was evaluated in 58 pts with clear cell histology dosed prior to Jul 1, 2013; 51 pts (88%) had an evaluable baseline PD-L1 IHC status. The ORR was 14% (8/58 PRs, 95% CI: 6, 25) and the median duration of response was 54 wks (2.7+ to 68.1+ wks). The 24-wk PFS rate was 53% (95% CI: 40, 66). An association was seen between PD-L1 intensity and response to MPDL3280A. Finally, antitumor activity that included immune-related responses was observed in non-clear cell histology pts (n = 10). Updated data including biomarkers will be presented. Conclusions: MPDL3280A was well tolerated, with no treatment-related deaths. Evidence of increased activity was observed in pts with elevated PD-L1. Durable responses and prolonged SD were observed in mRCC pts, warranting further study. Disclosure: D.F. McDermott: has participated in advisory boards for Genentech, BMS and Merck; M. Sznol: has consulted for Immune Design, Merus, Lion Biotechnologies, Kyowa-Kirin, Aztra-Zeneca-Medimmune, BMS, Amgen, Medimmune, Genentech, Symphogen, Nektar, and Anaeropharma; J. Soria: has received honoraria from Genentech and Roche; M.S. Gordon: has served in an advisory/consultant role and has received research funding from Roche/Genentech; O. Hamid: has been a speaker and consultant for Genentech, and research funding has been provided by Genentech; M. Fasso, Y. Wang, J. Bruey and G. Fine: is employed by Genentech. All other authors have declared no conflicts of interest.