Evolution of immune checkpoint inhibitor trials in oncology from 2011 to 2025: A cross-sectional study.

11048 Background: Immune checkpoint inhibitors (ICIs) have transformed the oncology therapeutic landscape since the first FDA approval in 2011. Over the past decade, ICIs have expanded rapidly across tumor types, disease settings, and therapeutic strategies. However, a comprehensive evaluation of the long-term evolution and key characteristics of global ICI clinical trials remains limited. We conducted a cross-sectional analysis to characterize temporal trends and fundamental features of ICI oncology trials registered on ClinicalTrials.gov from 2011 to 2025. Methods: All interventional oncology trials with a primary treatment purpose registered on ClinicalTrials.gov between January 1, 2011, and December 31, 2025, were included. ICI trials were defined as studies investigating agents targeting CTLA-4, PD-1, PD-L1, or next-generation immune checkpoints (e.g., LAG-3, TIGIT, TIM-3). Trials were categorized by phase, randomization, enrollment, funding source, geography, tumor type, treatment setting, and primary endpoints. Descriptive statistics summarized trial characteristics and temporal trends. Results: A total of 8,756 interventional treatment-purpose ICI trials were identified. Annual trial starts increased from 32 in 2011 to a peak of 955 in 2021, remaining consistently high thereafter (858 in 2022, 848 in 2023, and 817 in 2024), and reaching 940 in 2025. Most trials were Phase 2 (4,174/8,756; 47.7%), Phase 1 (1,756; 20.1%), or Phase 1/2 (1,374; 15.7%), while Phase 3 trials only accounted for 870 (9.9%) overall. The number of Phase 3 trials increased from 4 in 2011 to 100 in 2019, declined during 2020–2022, and subsequently rebounded to 101 in 2023, 110 in 2024, and a peak of 137 in 2025, reflecting ongoing maturation toward late-stage development. Funding was most frequently categorized as other (5,291; 60.4%), followed by industry (3,065; 35.0%) and US federal sources (400; 4.6%). The most common tumor groups were non–small cell lung cancer (NSCLC) (1,014; 11.6%), melanoma (579; 6.6%), breast cancer (498; 5.7%), and colorectal cancer (431; 4.9%). Among trials with available location data (n=8,152), the United States (4,173; 51.2%) and China (2,647; 32.5%) were the most frequent trial locations. Conclusions: Over the past 15 years, ICI clinical trials have expanded markedly in number and across tumor types; however, the majority remain early-phase, open-label, and small in scale, with Phase 3 studies comprising less than 10% of all trials. Encouragingly, the recent increase in late-phase trials suggests continued maturation of the immuno-oncology field and sustained progress toward regulatory approval. Persistent geographic concentration highlights the need to broaden global participation and strengthen the generation of confirmatory evidence to maximize the clinical impact of ICIs in cancer care.