Abstract Background: Lung cancer is frequently diagnosed in older adults. As the U.S. population continues to age, understanding treatment effects in lung cancer patients ≥65 years of age is increasingly important. Despite this trend, clinical trials (CTs) have historically under-enrolled older adults, creating a disparity between trial and real-world populations. Disproportionate enrollment can create challenges in understanding utilization in subpopulations. Due to increased interest in PD-(L)1 inhibitors for non-small cell lung cancer (NSCLC) treatment, CTs examining PD-(L)1 inhibitors in the first-line (1L) setting were selected to evaluate enrollment disparity in NSCLC immunotherapy. Methods: We identified 11 CTs that investigated 1L NSCLC anti-PD-(L)1 regimens submitted to the FDA between 2016 and 2020. Descriptive statistics were calculated based on the pooled dataset and compared with incident U.S. NSCLC cases diagnosed between 2015 and 2019, based on data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program. While SEER is a U.S. population-based representative sample, data from the trials included patients outside the U.S. that were submitted to support marketing applications with applicability to U.S. clinical practice. Results: A total of 7,030 patients enrolled in anti-PD-(L)1 CTs were included. In this sample, 48.2% were age ≥65 years, compared to 70.4% of incident U.S. NSCLC cases. This disparity persists with increasing age: 10.3% of enrollees were age ≥75 years and 0.5% of enrollees were age ≥85 years, compared to 34.3% and 7.2% of incident U.S. NSCLC cases, respectively. Discussion: Based on our results, older adults continue to be underrepresented in NSCLC anti-PD-(L)1 CTs, contributing to a potential treatment evidence gap. This gap widens with age and patients age ≥85 years constitute a miniscule portion (0.5%) of the CT cohort. Meanwhile, more patients will move into this group as the population ages. Aging can be associated with comorbidities and the potential for variance in patient and provider treatment preferences, which are important to acknowledge as these aspects may, in part, explain the results. Nonetheless, the gap in the number of older adults enrolled in this CT sample compared with SEER incidence demonstrates a clear need to improve recruitment in this underrepresented population. Awareness of trial-level and system-level barriers is necessary to minimize disparities. Additional research using tools such as real-world data to examine current treatment utilization, patient factors, and outcomes among underrepresented populations would increase the depth of evidence to address this disparity effectively. Citation Format: Felice Yang, Jonathon Vallejo, Oladimeji Akinboro, Catherine Lerro, Pallavi Mishra-Kalyani, Shenghui Tang, Paul G. Kluetz, Harpreet Singh, Donna R. Rivera. Enrollment of older adults in non-small cell lung cancer (NSCLC) clinical trials compared with population-based U.S. incidence [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr A024.