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PATHFINDER 2 is the US real-world study of the Galleri test that forms the core of its FDA submission.
PATHFINDER 2, trial NCT05155605 sponsored by GRAIL and reported in 2025, is the US real-world study of the Galleri multi-cancer blood test that forms the core of its FDA submission. It enrolled about 35,000 adults aged fifty or over who received Galleri alongside standard screening in a single-arm design, with 25,490 participants and one-year follow-up in the premarket approval application; a cancer signal was detected in about one percent, the positive predictive value was around sixty percent with very high specificity, and GRAIL reported at ESMO 2025 that adding the test found several times more cancers than standard screening alone. It improves on PATHFINDER 1, but the randomised NHS-Galleri trial did not meet its stage-shift endpoint, so whether detection translates into benefit is the open question.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
35,883 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Cancer signal detected | Galleri, all participants | 25,578 | 0.93% | - | - | link |
| Positive predictive value | Galleri | - | 61.6% | - | - | link |
| Specificity | Galleri | - | 99.6% | - | - | link |
A multi-cancer blood test can be run in ordinary clinics, and most positive results can be resolved with imaging. But six in ten positives are false alarms that take months to resolve, and the test misses most cancers. Whether it reduces late-stage cancer or deaths is unknown; that requires randomised trials.
NHS-Galleri is the trial that will decide whether a blood test for many cancers at once should be offered by a health system. Its endpoint is a reduction in late-stage cancer rather than deaths, so even a positive result leaves the mortality question to be settled by longer follow-up.
Shares Deborah Schrag, Eric A. Klein, Pre-agreed update rules so an MCED test is not obsolete when its trial reads out, Vanguard Study (NCI Cancer Screening Research Network).
Shares Cell-free DNA methylation tests, GRAIL, NHS-Galleri: design of the largest randomised trial of a multi-cancer blood test, PATHFINDER: the first prospective test of a multi-cancer blood test in people without symptoms.
Shares GRAIL, Galleri, Positive predictive value (PPV), Multi-cancer early detection (MCED).
Shares Cell-free DNA methylation tests, GRAIL, Galleri, Multi-cancer early detection (MCED).
Shares Cell-free DNA methylation tests, Galleri, Positive predictive value (PPV), Multi-cancer early detection (MCED).
Shares Vanguard Study (NCI Cancer Screening Research Network), NHS-Galleri: design of the largest randomised trial of a multi-cancer blood test, Multi-cancer early detection (MCED), The hardest cancers are found late.
Shares PATHFINDER: the first prospective test of a multi-cancer blood test in people without symptoms, Positive predictive value (PPV), Multi-cancer early detection (MCED), ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment.
Shares A whole-population cancer interception programme: risk-stratify every adult, detect and intercept early, Galleri, Multi-cancer early detection (MCED), The hardest cancers are found late.