Grail’s Galleri Multi-Cancer Blood Test Misses Primary Endpoint in Landmark NHS Trial

Grail’s Galleri Multi-Cancer Blood Test Misses Primary Endpoint in Landmark NHS Trial

The full results of the NHS-Galleri trial—the world’s first large-scale randomized controlled trial of a multi-cancer early detection (MCED) blood test—were presented by Charles Swanton of the Francis Crick Institute at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. While the trial demonstrated positive trends in detecting advanced Stage IV cancers, it failed to meet its pre-specified primary endpoint.¹

The Trial and the Primary Endpoint Failure

The trial, a partnership between the UK National Health Service (NHS) and Grail, enrolled 143,000 average-risk English adults aged 50–77. Participants were randomized to either usual care or annual screening with Grail's Galleri test, which analyzes epigenetic methylation patterns in circulating cell-free DNA (cfDNA) to spot cancer signals and predict their tissue of origin.

The primary endpoint was a reduction in combined Stage III and IV (late-stage) cancer diagnoses across all cancer types after three annual rounds of screening. The trial failed to meet this endpoint. In the first round of screening, the test detected many asymptomatic Stage III cancers that had not yet been clinically diagnosed. This initial "bump" in Stage III diagnoses offset subsequent reductions, preventing the combined late-stage rate from dropping significantly over the 3-year study period.

"The study’s main goal was to show a reduction in late-stage cancers overall, and this primary endpoint was not met... While Stage IV reduction signal, strengthening to 26% by the third screening round, is potentially meaningful, several confidence intervals cross 1.0, and the explanation for the Stage III increase in the first round that Stage IV cancers were being reclassified earlier is entirely speculative." — Professor Richard Houlston, Institute of Cancer Research, London (quoted in Science Media Centre)

Secondary Findings and Diagnostic Performance

Despite missing the primary endpoint, the trial yielded several clinically encouraging secondary outcomes:

• Stage IV Reduction: The test demonstrated a substantial and progressive reduction in highly lethal Stage IV cancer diagnoses, culminating in a 26% reduction by the third screening round.
• Early-Stage Shift: For a pre-specified group of 12 highly aggressive cancers, there was a noticeable shift toward detecting cases at earlier, more treatable stages (Stages I and II).
• High Specificity and Low False Positives: The test maintained a specificity of 99.55% and a positive predictive value (PPV) of 52.0%. This means that more than half of the asymptomatic individuals who received a positive blood test were indeed confirmed to have cancer—a vast improvement over traditional diagnostic referrals, where only about 6% of urgent referrals result in a cancer diagnosis.
• Cancer Signal of Origin (CSO): The test predicted the primary site of the cancer with 92.5% accuracy, providing clinicians with a clear pathway for follow-up diagnostic scans.

Expert Critiques and Policy Implications

Oncology and public health experts are divided on the test’s immediate utility. Advocates point to the progressive drop in Stage IV diagnoses as a signal that long-term, multi-year screening could eventually reduce cancer mortality. However, critics argue that the failure of the primary endpoint, coupled with the test’s low sensitivity for early-stage (Stage I and II) cancers, makes population-scale deployment unjustified at this time.

Furthermore, rolling out the test across the NHS could overwhelm already strained diagnostic services:

"Expanding this kind of testing at population scale would place massive pressure on already stretched diagnostic services at a time when the NHS is struggling to meet cancer waiting-time targets...² on the basis of results from this and smaller trials, there is no evidence base upon which to justify implementation of Galleri at a population scale." — Professor Richard Houlston, Institute of Cancer Research, London (quoted in Science Media Centre)

Definitive conclusions regarding the test's clinical benefit will require longer-term follow-up and the release of overall mortality data, which are expected in the next few years.