⭐️⭐️⭐️🚨Looking forward to presenting this #Tumor agnostic landscape project @myESMO MADRID. Please come by poster and say 👋 ⭐️4294P - The tumor-agnostic (TA) therapy biomarker landscape: Established and emerging markers across 385,420 solid tumors Presentation Number #4294P Date Fri, 23.10.2026 Time 15:15 - 16:00 Abstract Background TA approvals have increasingly been granted by the FDA for molecularly-guided cancer therapies. With a growing number of therapies under investigation in pan-tumor trials, we assessed the real-world landscape of currently approved (cTA) and emerging (eTA) biomarkers in a cohort of patients (pts) tested with comprehensive genomic profiling (CGP). Methods The prevalence of biomarkers associated with current and potential future TA indications was assessed across 385,420 solid tumor samples from unique pts profiled with FoundationOne®CDx. Across 196 active Ph1 or 2 pan-solid tumor trials evaluating 213 unique therapies, 105 enrollment biomarkers were assessed for TA potential. eTA biomarkers included those associated with a multi-tumor ORR ≥ 20% with responses in ≥4 tumor types: ALK rearrangements, ERBB2 mutations [muts]/amplifications [amps], FGFR2 alterations, MET amps/fusions, NRG1 fusions, KRAS/HRAS muts, TP53 Y220C, and MTAP loss. HER2 IHC status was not available for this cohort. Results 18.7% of solid tumor pts had a cTA (1.8% BRAF V600E, 0.2% RET fusion, 0.1% NTRK fusion, 13.8% TMB-high, 0.1% MSI-high, 2.8% multiple) and an additional 31.7% of cTA-negative pts were eTA-positive (14.0% KRAS, 5.5% MTAP, 4.2% ERBB2, 2.9% others, 5.1% multiple), for a potential future TA biomarker prevalence of 50.4%. The largest potential increase in TA biomarker prevalence was in pancreatic (86.6%; 6.7% with biomarkers currently approved in-tumor type [ITT] or cTA to 93.3% with ITT, cTA, or eTA), small intestine (63.5%, 13.9% to 77.3%), and gallbladder (49.4%, 5.9% to 55.3%). CRC (96.5%), pancreatic (93.3%), melanoma (83.5%), and NSCLC (77.5%) had the highest resulting combined prevalence. eTA biomarkers with greatest impact on prevalence were KRAS in CRC (91.7% of ITT/cTA-negative samples), pancreatic (88.3%), and small intestine (56.6%); and MTAP in GBM (46.6%) and pancreatic (34.6%). Conclusions The expansion of approved TA indications, coupled with accelerating druggability of once-intractable targets, stands to fundamentally reshape treatment for cancers currently lacking targeted options. The breadth and cross-tumor prevalence of eTA biomarkers underscore CGP as an essential tool for clinical decision making @JiaJennyLiu @JulianaRBeal @niamhjcoleman @FoundationATCG @BenWestphalen @curijoey @chadinabhan @OncoAlert @oncodaily