Abstract LB-B005: No effect of the time-of-day infusion of adjuvant pembrolizumab in the outcomes of patients with resectable melanoma in the NCI/SWOG trial S1404

Abstract Background: Multiple reports have suggested that receiving immunotherapy infusions “earlier” in the day is associated with improved outcomes, including longer overall survival and lower toxicity rates. However, the definition of “early” varies between publications. Reports also fail to account for confounding factors (including distance to infusion center), are subject to survivor bias (analyzing post-baseline factors at baseline), and do not adjust p-values for multiple comparisons when evaluating multiple potential thresholds for early versus late time-of-day of infusion. Methods: We analyzed a previously reported multi-center clinical trial evaluating pembrolizumab as adjuvant therapy for patients with resectable high-risk melanoma. Standard statistical methodologies that account for potential biases were used to evaluate the association between time-of-day of infusion and clinical outcomes. Results: 628 participants received pembrolizumab and had time of first infusion recorded. Median age was 55 years, range 20-82. Odds of infusion before 11:00 hours increased by 32% over 12 months of therapy (p=0.013). Participants living further from their treating institution had later infusion times on average: odds of infusion before 11:00 decreased by 9% for each additional 50 miles (p=0.017). The optimal cut-point for first infusion time for OS was 15:48 with hazard ratio (HR)=1.40; changing the cut-point by 30 minutes earlier to 15:18 decreased HR to 0.98, indicating lack of robustness of the threshold. No significant association was identified between proportion of early infusions and outcomes in multivariable time-dependent Cox regression models. Conclusions: In this multi-center trial of adjuvant pembrolizumab for patients with high-risk melanoma, analyses that account for common sources of bias found no significant association between recurrence-free or overall survival and time-of-day of infusion. Clinical trial identification: NCT02506153 Funding: NIH/NCI grants U10CA18088, U10CA180819 Citation Format: Megan Othus, Thach-Giao Truong, Elad Sharon, Kari Kendra, Kenneth Grossman, Elizabeth Buchbinder, Nikhil Khushalani, Zeynep Eroglu, Sunandana Chandra, Gary Doolittle, John M. Kirkwood, Alexandra P. Ikeguchi1, Catalin Mihalcioiu, C. Lance Cowey, Sunil A. Reddy, Douglas B. Johnson, Matthew Taylor, Vernon K. Sondak, Antoni Ribas, Sapna P. Patel. No effect of the time-of-day infusion of adjuvant pembrolizumab in the outcomes of patients with resectable melanoma in the NCI/SWOG trial S1404 [abstract]. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr LB-B005.