Background: Avelumab* is a fully human anti-PD-L1 IgG1 antibody showing preliminary efficacy in multiple tumor types. We report updated safety data of single-agent avelumab in patients (pts) with locally advanced or metastatic (LA/M) solid tumors from a phase 1b trial (NCT01772004). Methods: Pts from 16 different expansion cohorts (including NSCLC, gastric, ovarian, urothelial, mesothelioma, and breast), all unselected for PD-L1 expression, received avelumab 10 mg/kg IV Q2W until progression, unacceptable toxicity, or withdrawal. Treatment-emergent adverse events (AEs) were graded by NCI-CTCAE v4.0. Results: As of Nov 5, 2015, 1,300 pts received avelumab and were followed for ≥ 4 wks. Median age was 63 y (range 20-91), ECOG PS was 0 (37.7%), 1 (62.1%), or 2-3 (0.2%), and median number of prior lines of anticancer therapy was 2 (range 1-13). Median duration of treatment with avelumab and number of administrations were 11.5 wks (range 2-104) and 5 infusions (range 1-50), respectively. Treatment-related (TR) AEs occurred in 813 pts (62.5%), and the most common ( ≥ 5%) were fatigue (n = 212, 16.3%), infusion-related reaction (IRR; n = 209, 16.1%), nausea (n = 108, 8.3%), chills (n = 102, 7.8%), diarrhea (n = 79, 6.1%), and pyrexia (n = 72, 5.5%). Grade ≥ 3 TRAEs occurred in 124 pts (9.5%). The most frequent ( ≥ 0.5%) grade ≥ 3 TRAEs were GGT elevation (n = 9, 0.7%), IRR (n = 9, 0.7%), fatigue (n = 8, 0.6%), lipase elevation (n = 8, 0.6%), anemia (n = 7, 0.5%), and dyspnea (n = 6, 0.5%). Potential immune-related (ir) TRAEs were reported for 93 pts (7.2%); the most frequent ( ≥ 1.0%) were hypothyroidism (n = 45; 3.5%) and pneumonitis (n = 13; 1.0%). TRAEs resulted in permanent discontinuation for 79 pts (6.1%): 25 (1.9%) due to an IRR and 14 (1.1%) due to a potential irTRAE. TRAEs were considered the primary cause of death by the investigator for 5 pts (0.4%): radiation pneumonitis (1), pneumonitis (1), autoimmune hepatitis/liver failure (2), and respiratory distress/sepsis (1). Conclusions: Single-agent avelumab showed an acceptable safety profile in a heavily pretreated population and large dataset of pts with LA/M malignancies. Additional analyses and phase 3 trials are ongoing. *Proposed INN. Clinical trial information: NCT01772004