Background: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with poor prognosis. Studies of second-line chemotherapy for metastatic MCC (mMCC) have reported median progression-free survival (PFS) of up to 3 months and no benefit to overall survival (OS). Avelumab, a human anti–PD-L1 monoclonal antibody, is approved in several countries for the treatment of mMCC. Here, we report updated efficacy and safety data from part A of the pivotal, single-arm, phase 2, JAVELIN Merkel 200 trial of avelumab in patients (pts) with mMCC and ≥2 y of follow-up. Methods: Pts with mMCC and progression on prior chemotherapy received avelumab 10 mg/kg intravenously every 2 weeks until disease progression or intolerable adverse event (AE). Objective response rate (ORR), duration of response (DOR), and PFS were evaluated by independent review per RECIST v1.1; OS and AEs (per NCI CTCAE v4.0) were also evaluated. Results: As of Sep 26, 2017, 88 pts were followed for a median of 29.2 mo (range 24.8-38.1). The median duration of treatment was 3.9 mo (range 0.5-36.3); treatment was ongoing in 9 pts (10.2%). The confirmed ORR of 33.0% (95% CI 23.3-43.8; complete response in 11.4%) remained unchanged from previous analyses at 1 y and 18 mo; responses were ongoing in 19 of 29 pts, including 12 pts with > 2 y response duration. Median DOR had not been reached (range 2.8-31.8 mo; 95% CI 18.0-not estimable). Durable responses led to stable rates of PFS (29% at 1 y, 29% at 18 mo, and 26% at 2 y). Median OS was 12.6 mo (95% CI 7.5-17.1) and the 2-y OS rate was 36% (50% at 1 y and 39% at 18 mo). Clinical activity was observed across all pt subgroups, irrespective of tumor PD-L1 and MCPyV status. The AE profile remained consistent with previous analyses: 67 pts (76.1%) had a treatment-related AE (TRAE), 10 pts (11.4%) had a grade ≥3 TRAE, 20 pts (22.7%) had an immune-related AE, and no treatment-related deaths occurred. Conclusions: At ≥2 y of follow-up, avelumab shows continued durable responses and meaningful survival outcomes in pts with mMCC, exceeding the outcomes associated with cytotoxic chemotherapy. Efficacy and safety results confirm the lasting clinical benefit of avelumab in pts with mMCC. Clinical trial information: NCT02155647