Background: Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer. Tumor oncogenesis is linked to Merkel cell polyomavirus (MCPyV) integration and UV exposure. PD-L1 is often expressed in MCC tumors, suggesting that patients with MCC could benefit from anti-PD-L1 therapy. Avelumab is a fully human anti-PD-L1 IgG1 monoclonal antibody that has demonstrated clinical efficacy in patients (pts) with metastatic MCC (mMCC) in a Phase 2 trial with an objective response rate (ORR) of 31.8% in the primary analysis. Assessment of candidate predictive biomarkers may help to identify patients with a greater probability of response to avelumab and to improve understanding of MCC biology. Methods: Patients in a Phase 2 trial (NCT02155647) with mMCC and tumor progression on prior chemotherapy received avelumab at 10 mg/kg Q2W. PD-L1 expression, MCPyV status and CD8+ T-cell infiltration in pretreatment tumor samples were evaluated by immunohistochemistry (IHC). MCPyV status was also evaluated by real-time PCR. Results: Tumor PD-L1 expression was evaluable in 74 of 88 (84.1%) pts with mMCC treated with avelumab, of which 58 (65.9%) and 19 (21.6%) pts were positive at 1% and 5% cut-offs. ORR was 34.5% and 18.8% for PD-L1 positive and negative pts at 1% cutoff, and 52.6% and 23.6% for PD-L1 positive and negative pts at 5% cutoff. MCPyV status was positive in 60% (46/77) pts evaluable by IHC and 63% (45/71) pts evaluable by PCR; of 66 pts tested by both IHC and PCR, concordance was 90.9%. MCPyV+ and MCPyV– pts had similar frequencies of PD-L1+ tumors (80% and 73%) with an ORR of 26.1% and 35.5% respectively. Baseline CD8+ T-cell infiltration was assessed at tumor invasive margin and tumor center in 53 pts, ORR was 44.4% vs 19.2% and 32.1% vs 28% for pts with high or low CD8+ T-cell density at respective locations. Conclusions: In an international cohort of pts with mMCC, avelumab had clinical activity among biomarker subgroups analyzed, including PD-L1 expression, MCPyV status and density of CD8+ tumor-infiltrating T-cells. The current biomarkers were not predictive of response but further research into understanding how avelumab mediates anti-tumor activity in MCC may identify novel biomarkers. Clinical trial information: NCT02155647