GRAIL (GRAL) Study result summary

Study design and scope

• NHS-Galleri was the first randomized controlled trial of an MCED, enrolling over 142,000 participants aged 50–77 in England, randomized 1:1 to Galleri plus standard care or standard care only, with three annual screening rounds and ongoing follow-up.

• PATHFINDER 2, the largest interventional MCED study in North America, enrolled about 36,000 participants aged 50+ from 32 healthcare systems, with up to three years of follow-up.

Key endpoints and findings

• The primary endpoint in NHS-Galleri was reduction in combined stage III/IV cancers for 12 deadly cancers; secondary endpoints included reduction in stage IV cancers, increase in stage I/II cancers, test performance, and safety.

• NHS-Galleri showed a >20% reduction in stage IV cancers in incident rounds, a 16% increase in stage I/II cancers, and a 21% reduction in clinically detected cancers.

• Fourfold increase in screen-detected cancers and >25% reduction in emergency-presenting cancers were observed with MCED addition.

• No statistically significant reduction in combined stage III/IV diagnoses for the 12 cancers in the primary endpoint, partly due to prevalent late-stage cancers in the first round.

Test performance and safety

• Galleri's PPV was 52% overall (58% in the first round), specificity 99.55%, false positive rate 0.45%, and NPV nearly 99%.

• Cancer Signal of Origin accuracy was 92.5%; episode sensitivity 54.7% for the 12 deadly cancers.

• Most diagnostic procedures following a positive test were non-invasive, and invasive procedures were more common in participants with cancer.

• No serious study-related adverse events were reported, confirming a strong safety profile.