NHS-Galleri Trial Misses Primary Endpoint but Shows 26% Reduction in Stage IV Cancer by Third Round
The NHS-Galleri trial of the Galleri multi-cancer early detection test did not meet its primary endpoint of reducing combined Stage III-IV cancers. Secondary results showed a 26% reduction in Stage IV diagnoses by the third screening round for 12 deadly cancers. The test increased cancer detection rates four-fold compared to standard screening alone.
The landmark NHS-Galleri randomized controlled trial of the Galleri multi-cancer early detection test failed to meet its primary endpoint of a statistically significant reduction in combined Stage III and IV cancers, but secondary results showed a substantial and progressive reduction in Stage IV diagnoses with repeated screening. The trial, which enrolled 142,000 demographically representative NHS participants aged 50 to 77 over three years, found that adding annual Galleri screening to standard of care increased cancer detection rates four-fold while reducing late-stage and emergency diagnoses.
The primary endpoint of a statistically significant Stage III-IV reduction was not met after three rounds of screening. However, for the pre-specified group of 12 deadly cancers, the relative incidence rate of combined Stage III/IV cancers was 1.03 (95% CI: 0.92, 1.14; p=0.6324) after three rounds. In contrast, Stage IV diagnoses decreased with each sequential screening round, showing a 9% reduction in the first round, a 22% reduction in the second round, and a 26% reduction in the third round.
The addition of the Galleri test to standard screening led to a four-fold increase in the overall cancer detection rate compared to standard of care screening alone in England for breast, colorectal, cervical, and high-risk lung cancer. There was also a 16% increase in the absolute number of Stage I-II cancers diagnosed across the 12 pre-specified deadly cancer types that are typically found in late stages. Screening resulted in a 25% decrease in cancers diagnosed after emergency presentation, which are associated with higher mortality and healthcare costs.
Test performance metrics remained consistent with those previously reported from North American studies. Over the three screening rounds, 0.91% of participants had a positive MCED test result, with a cancer detection rate of 0.48%. The positive predictive value was 52.0% overall and 58.0% in the first screening round. Specificity was 99.55%, resulting in a false positive rate of 0.45%. The Cancer Signal of Origin accuracy was 92.5%, and episode sensitivity—the ability to detect cancers diagnosed within 12 months after each screening blood draw—was 54.7% for the 12 prespecified cancer types and 30.7% across all cancer types.
No serious adverse events related to the Galleri test were reported in the trial. The results demonstrate that multi-cancer early detection can shift the stage at which cancers are detected at a population level, increasing the opportunity for curative treatment, particularly for Stage III cancers. The company stated that the findings provide its strongest argument to date for the clinical benefit of the test and noted that it is expanding its U.S. sales and medical teams based on the results.
The U.S. Food and Drug Administration's premarket approval application for the Galleri test is pending review and includes metrics from the NHS-Galleri trial focused on test performance, clinical validation, and the clinical benefit of detection at Stages I through III. While the trial missed its primary endpoint, the Stage IV reduction data may inform regulatory discussions. In the interim, the company will likely need to provide overall survival data to gain a full label indication for population-level screening, and the trial results will be submitted for publication in a peer-reviewed medical journal.