Background: The programmed death-1 receptor (PD-1) and its ligand (PD-L1) are key therapeutic targets in the reactivation of the immune response against multiple cancers. Avelumab* (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody currently being investigated in clinical trials. Methods: This is a parallel group expansion trial of avelumab in patients (pts) with selected tumor indications following the determination of dose and regimen in a phase I, open label, dose escalation study. The dose escalation cohort has been completed (n = 53). Pts in 11 separate cohorts of advanced solid tumors will receive avelumab at 10 mg/kg as a 1h infusion, Q2W. Treatment will continue until disease progression, unacceptable toxicity, or if any criterion for withdrawal of investigational medicinal product occurs. In addition to evaluating tolerability, specific objectives for the expansion cohorts include: assessment of best overall response (BOR) and progression-free survival (PFS) according to RECIST 1.1; assessment of immune-related BOR and immune-related PFS using the modified Immune-Related Response Criteria; and assessment of overall survival. Association between tumor PD-L1 expression and efficacy will be evaluated and the PK/PD profile of avelumab characterized. This trial is in progress: recruitment for 2^nd-line non-small cell lung cancer (n = 184), metastatic breast cancer (n = 168), colorectal cancer (n = 21), and ovarian cancer cohorts (n = 75) is complete. Recruitment for gastric/gastroesophageal junction cancer (n = 150), melanoma (n = 50), castration-resistant prostate cancer (n = 20), adrenocortical carcinoma (n = 50), mesothelioma (n = 50), urothelial carcinoma (n = 50), and 1^st-line NSCLC (n = 150) is ongoing (target enrollment provided for each tumor type). Overall, > 700 pts have been enrolled across the dose escalation and current expansion cohorts (start Jan 2013, estimate end Oct 2016). NCT01772004. *Proposed INN. Clinical trial information: NCT01772004