e21070 Background: There is little data on quality of life (QoL) for patients (pts) with Merkel cell carcinoma (MCC). To better understand how new treatments might impact QoL in MCC, pts with stage IV chemotherapy-treated MCC from a single-arm, open-label, multicenter, international phase 2 trial (NCT02155647) of a novel immunotherapy were followed for QoL and clinical outcomes. Methods: Because there is no MCC-specific QoL instrument, the FACT-Melanoma (FACT-M), a validated QoL questionnaire including multiple subscales and summary scores (Trial Outcome Index [TOI], FACT-G total and FACT-M total) was used. Pts completed the FACT-M at baseline (BL), week 7, every 6 weeks until disease progression (PD) and at end of treatment (EOT). Linear mixed models (LMM) were fitted for change from BL for each scale including the time-varying covariate PD vs non-PD. Established minimal important differences (MID) were used to interpret meaningfulness of changes. Sensitivity analyses explored the effects of missing data. Results: 70 pts were analyzed. Overall, no meaningful changes from BL were observed for each scale during treatment. Moderate correlations between reduction in tumor size and improvements in FACT-M were observed at week 7 for Functional Well-being (-0.47), TOI (-0.36), FACT-M total (-0.36), and FACT-G total (-0.34), suggesting improvements in QoL with tumor shrinkage. LMM showed differences between PD vs non-PD groups in the range of MIDs for Functional Well-being (2.23, p = 0.018), Melanoma (3.19, p = 0.012), Surgery (1.95, p = 0.109), TOI (6.36, p = 0.012) and FACT-G total (3.89, p = 0.105). These models showed improvement for the non-PD group in Emotional Well-being (1.55, p = 0.004) and worsening for the PD group in Physical Well-being (-1.63, p = 0.041), Surgery (-2.09, p = 0.044) and TOI (-4.56, p = 0.036). As expected, all scales worsened in the range of MIDs at EOT, mostly due to PD. Sensitivity analyses were consistent, with modest increases in estimated differences. Conclusions: In pts with metastatic MCC, non-progression during avelumab treatment contributed to statistically and clinically meaningful improvements in health-related QoL. Clinical trial information: NCT02155647.