Background: Response rates are key efficacy endpoints in oncology trials, yet correlations with OS are not universal across cancer types. MCC is a rare and aggressive skin carcinoma, although it is chemo sensitive with high response rates, responses are of short duration with no demonstrated benefit to OS. This study explores the association between OR and OS in mMCC pts treated with the anti-PD-L1 avelumab. Methods: Efficacy data with ≥ 18 months of follow-up from Part A of the phase II avelumab trial (NCT02155647) were analyzed. Pts had prior progression on or after chemotherapy and received avelumab 10 mg/kg IV Q2W until confirmed progression, unacceptable toxicity, or withdrawal. Tumors were assessed for OR every 6 weeks (RECIST v1.1). Using conditional landmark analyses, OS was compared between pts with and without an independently confirmed OR up to day 47. Only pts alive at the landmark (day 47) are included in this analysis. In a sensitivity analysis, a landmark of 89 days was used. A Cox model including OR as a covariate was fit (unadjusted, controlling for age, visceral disease, and number of previous therapies). Results: 20 pts had an initial OR reported up to day 47, with 7 further pts having an OR between day 48 and day 89, and 2 pts having an OR after day 89, including 10 complete responses (CRs). 5 pts died and 1 withdrew consent before day 47 (all without OR). Survival probabilities 18 months after treatment initiation were 0.900 (95%CI: 0.656; 0.974) for pts with OR up to day 47 vs. 0.262 (95% CI 0.157; 0.378) for pts without OR but alive up to day 47. Similar results were observed for the 89-day landmark. In the unadjusted Cox model, OR was associated with a 94% risk reduction of death (hazard ratio: 0.064 [95% CI: 0.022; 0.181]). The hazard ratio in the adjusted model was 0.052 (95% CI: 0.018; 0.152). Conclusions: Avelumab therapy for previously treated mMCC pts demonstrated a clinically relevant and high survival impact. For avelumab, OR was associated with long-term survival, likely driven by the rapid time to response, substantial tumor reductions including CRs and sustained durable responses not reported in the chemotherapy literature for mMCC. Clinical trial information: NCT02155647