Background: Avelumab* is a fully human anti-PD-L1 IgG1 antibody under clinical investigation in multiple cancers. We report safety and clinical activity of single-agent avelumab in patients (pts) with metastatic adrenocortical carcinoma (mACC), a rare malignancy for which there are limited therapeutic options (NCT01772004). Methods: Pts with mACC who had progressed after platinum-based therapy and were unselected for PD-L1 expression were treated with avelumab at 10 mg/kg IV Q2W until progression, unacceptable toxicity, or withdrawal. Prior and ongoing treatment with mitotane was permitted. Tumors were assessed every 6 wks (RECIST 1.1). Objective response rate (ORR) and progression-free survival (PFS) were evaluated. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Results: As of Oct 23, 2015, 37 pts were treated with avelumab (median 8 wks [range 2-48]) and followed for a median of 13 wks (range 0-58). Median age was 50 y (range 23-71), ECOG PS was 0 (37.8%) or 1 (62.2%), and median number of prior treatments for metastatic disease was 1 (range 0-5). Treatment-related (TR) AEs occurred in 23 pts (62.2%); the most common (> 10%) were nausea (6 [16.2%]), fatigue (5 [13.5%]), pyrexia (5 [13.5%]), and infusion-related reaction (5 [13.5%]), all of grade 1/2. Grade ≥3 TRAEs occurred in 5 pts (13.5%; each 1 event): hyperkalemia, increased ALT, GGT, or transaminase, sepsis, spinal cord infection, and pneumonitis. Potential immune-related TRAEs occurred in 4 pts (10.8%): 3 pts with grade 1/2 events and 1 pt with grade 3 pneumonitis that resolved. There were no treatment-related deaths. Among 19 pts with ≥13 wks f/u, unconfirmed ORR was 10.5% (2 partial responses; 95% CI: 1.3, 33.1). Stable disease was observed in 5 pts (26.3%); disease control rate was 36.8% (7/19). Median PFS was 7.6 wks (95% CI: 5.9, 23.9), and PFS rate at 12 wks was 30.3% (95% CI: 12.3, 50.7). Conclusions: Avelumabshowed an acceptable safety profile and clinical activity in pts with mACC, a dataset representing the first study to date of an anti-PD-(L)1 agent in this rare tumor type. Analyses of activity, including response correlated with PD-L1 expression, are ongoing. *Proposed INN. Clinical trial information: NCT01772004