Abstract Objectives: Body weight is an important prognostic factor in patients with lung cancer. As immunotherapy involves toxicities, body weight may be affected during the treatment course. The objective of this study is to examine the trajectory of weight changes at 180 and 365 days after the initiation of immune checkpoint inhibitors (ICIs) among patients with NSCLC. Methods: Retrospective chart review and data extraction were performed among patients receiving ICIs at the Ohio State University Comprehensive Cancer Center between 2015 and 2021. Patients with NSCLC were included in this study if their initial treatment entailed a PD-1/PD-L1 ICI), either alone or in combination with chemotherapy/targeted cancer drugs, and if they also had their body weights recorded on ICI initiation and 180 days after (± 30 days) treatment initiation. A subset of these patients who had body weight data on day 365 of ICI initiation were included in additional analysis. Percentages of change in body weight relative to pre-ICI were calculated ([weight at 180 or 360 days minus pre-ICI weight] divided by pre-ICI weight x 100%) and examined by treatment regimen and pre-ICI body mass index (BMI) using t-tests. A sensitivity analysis was performed by excluding 11 patients with cachexia defined by the presence of ICD-9 (799.4) or 10 (R64) codes in their medical records. Results: A total of 554 patients with NSCLC received any ICI; 139 patients met the inclusion criteria, of which 96 had body weight data on day 365. The mean age of diagnosis was 63.8 (SD=10.1); 80% were White and 18.7% were Black. The median time on ICI was 195 days (inter-quartile range, 55-392 days) among patients with ICI only and 255 days (inter-quartile range, 126-479 days) among patients with ICI combined with chemotherapy or targeted cancer drugs. Among patients receiving ICI only, body weight increased among those with normal weight (BMI <25.0; mean change = +7.57%, P=0.013) but decreased among those classified as overweight (BMI = 25.0 to 29.9; −5.2%, P=0.037) or obese (BMI ≥30; −6.5%, P=0.025). Decreases in weight were also observed for patients with obesity and receiving a combined treatment (−9.65%, P=0.043). After one year of treatment, weight changes among patients receiving ICI only remained significant in the normal weight group (+15.6%, P=0.007), but not among patients with other BMIs and treatment regimens. These associations remained similar after excluding the patients with cachexia. Conclusions: Body weight change during ICI therapy may vary by treatment regimen and pre-ICI BMI among patients with NSCLC. Whether the weight changes are related to toxicities and survival warrants further research to shed light on weight management, ICI efficacy, and prevention of treatment-related adverse events. Funding: The study was in part funded by NIH/NCI R37CA248371, OSUCCC CCSG P30CA016058, and Pelotonia Institute for Immuno-Oncology (PIIO) at OSUCCC. Citation Format: Ting-Yuan David Cheng, Ben Kinder, Rand T. Akasheh, Cuthbert Mario Mahenge, Carolyn J. Presley, Peter G. Shields, Xuan Nguyen, Aditi Shendre, Zihai Li, Lang Li. Body weight trajectory among patients with non-small-cell lung cancer receiving immune checkpoint inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3404.