COPE ctDNA Profiling Raises Genotyping to 97%, but Does Not Improve 18-Month OS

COPE tested serial ctDNA profiling with FoundationOne Liquid CDx plus centralized molecular tumor board review versus tissue profiling and standard imaging in an open-label, randomized, non-comparative Phase 2 trial in stage IIIB/IV NSCLC (n=176; NCT04258137). The ctDNA arm improved baseline genotyping success from 69% with tissue alone to 97% with tissue+plasma by rescuing 32/35 tissue-insufficient cases, but 18-month OS was 53.8% in the ctDNA arm versus 65.7% in the control arm, with median OS 22.4 months. In an exploratory 1L chemo-immunotherapy subset with paired baseline/week-3 samples (n=90 evaluable), day-21 ctDNA clearance tracked with higher ORR (81.8% vs 50.0%), longer median PFS (22.9 vs 5.9 months), and higher 18-month OS (81.8% vs 57.1%), but this remains biomarker-prognostic rather than proven treatment-changing compared with KEYNOTE-189-style chemo-IO benchmarks.