24,000 多项免疫肿瘤学试验中生物标志物应用的时间趋势

As immuno-oncology (IO) matures beyond the checkpoint inhibitor era, understanding how biomarker-informed trial design is evolving along with therapeutic diversification is important for optimizing future development decisions. The Cancer Research Institute (CRI) has built a comprehensive IO clinical trial database, capturing global activity across cancer types and therapeutic modalities [1]. Here, we leveraged this resource to analyze temporal trends in IO therapeutic development and biomarker adoption to reveal how the field is evolving over time. We curated over 24,000 interventional IO clinical trials (data cut-off: June 2025), extracting therapeutic modality, molecular targets, cancer indication, trial phase, sponsor type, and biomarker data. We analyzed temporal trends in trial initiation, modality, and biomarker usage. Biomarkers (n=9,849) were classified by molecular type, functional role, and indication-specific usage patterns. The IO landscape shows clear maturation with over 10,000 currently active trials dominated by phase II studies. While checkpoint inhibitors remain dominant, IO drug target diversity has significantly increased, driven primarily by multi-target combinations designed to overcome resistance. Furthermore, biomarker strategies show striking differences across cancer types. Hematologic malignancies lead in biomarker usage, with about 65% adoption and 31% dual selection/monitoring use, compared to solid tumors (58% and 23% respectively). Among solid tumors, respiratory cancers show the highest adoption at around 66%, driven by established markers like PD-L1 and driver mutations, while gastrointestinal cancers lag at about 50% despite representing the largest trial volume. Protein biomarkers dominate at over 80% of total, with tumor mutational burden and microsatellite instability markers emerging as pan-cancer standards. Notably, biomarker usage dropped below 50% in 2024 for the first time since 2012. This may reflect how the field's strategy is shifting: pursuing broader patient populations while also developing smarter multi-marker approaches for specific indications, representing an important turning point in IO development. The updated CRI IO landscape database, which integrates global IO clinical trial activity and biomarker utilization, gives the research community a unique look into how immunotherapy is evolving, helping investigators and sponsors see where their work fits in the bigger picture, spot emerging trends, and identify areas where biomarker development hasn't kept pace with new therapies. These landscape insights are important for making better decisions about where to invest resources and effort to have the greatest patient impact. Reference 1. Benthani F, Upadhaya S, Zhou A. Cancer cell therapies: Global clinical trial trends and emerging directions. Nature Reviews Drug Discovery.