FDA Advisory Committee to Review Premarket Approval Application for Multi-Cancer Early Detection Test

The FDA’s Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee will meet on September 23, 2026, to review the premarket approval application for the Galleri multi-cancer early detection (MCED) blood test.¹

The test is designed to detect cancer-specific methylation patterns shared across many cancer types before symptoms appear, including for cancers that lack recommended screening today, and to predict the cancer signal origin to help guide diagnostic evaluation.

GRAIL submitted the premarket approval application to the FDA on January 29, 2026. Previously, the FDA designated Galleri as a breakthrough device in 2018. The premarket approval submission is based on performance and safety results from 25,490 participants with 1 year of follow-up in the PATHFINDER 2 study and more than 70,000 participants in the prevalent-round intervention arm of the NHS-Galleri trial.

“Galleri is the only MCED test supported by large interventional and randomized, controlled studies in intended-use populations,” Josh Ofman, MD, MSHS, chief executive officer of GRAIL, stated in a news release. “We appreciate the FDA’s leadership in advancing the review of the first premarket approval application for an MCED, and we look forward to discussing Galleri’s clinical data and the opportunity for MCED to address a significant unmet public health need with the Advisory Committee.”

The Galleri test is intended to be used in addition to, not as a replacement for, guideline-recommended screenings.

What did the PATHFINDER 2 study show?

PATHFINDER 2 was described by investigators as the largest interventional MCED study conducted in an intended-use population in North America to date; 35,878 participants (median age, 64 years; range, 58-70) were enrolled, with 32,007 individuals in the performance-analyzable cohort, according to data presented at the 2026 ASCO Annual Meeting.²

Over 12 months of follow-up, the test demonstrated a positive predictive value (PPV) of 60.3% (95% CI, 54.5%-65.8%), a specificity rate of 99.6% (95% CI, 99.6%-99.7%), and an episode sensitivity rate of 39.3% (95% CI, 34.9%-44.0%) across all cancers, rising to 69.8% (95% CI, 62.8%-76.0%) for the 12 cancers responsible for a majority of US cancer deaths. Among MCED-detected new primary cancers, 53.0% were diagnosed at stage I to II, and 67.6% were types without US Preventive Services Task Force (USPSTF) grade A/B/C screening recommendations.

What were the primary results of the NHS-Galleri trial?

NHS-Galleri is the largest and only randomized, controlled clinical utility trial of an MCED test conducted to date.³ A total of 142,826 consented participants ages 50 to 77 years with no cancer diagnosis or treatment in the prior 3 years were randomly assigned 1:1 to an intervention arm (n = 71,122), in which MCED testing was performed and results returned, or a control arm (n = 71,128), in which samples were stored. The primary end point was a significant reduction in the incidence of late-stage (stage III/IV) cancer after 3 annual screening rounds.

The primary end point was not met. After 3 screening rounds, 706 stage III/IV cancers were diagnosed in the intervention arm vs 688 stage III/IV cancers in the control arm across 12 prespecified cancer types (incidence rate ratio [IRR], 1.03; 95% CI, 0.92-1.14; P = .6324). Investigators reported that the null result appeared to be driven by an increase in the numbers of stage III diagnoses from the investigational arm (n = 364) to the control arm (n = 291), whereas the numbers of stage IV diagnoses decreased from the investigational arm (n = 397) to the control arm (n = 342).

For the prespecified secondary end point of stage IV incidence among the 12 cancer types, the intervention arm showed an IRR of 0.86 (95% CI, 0.744-0.998), a 14% reduction that deepened to 22% and 26% in the second and third (incident) screening rounds, respectively. A shift toward earlier-stage detection was also observed, with a 16% increase in the number of stage I to II diagnoses (647 vs 559; relative risk, 1.16; 95% CI, 1.03-1.30).

What safety and performance data supported the premarket approval application submission of the Galleri MCED test?

In NHS-Galleri, aggregate MCED test performance over 3 screening rounds included a PPV of 52.0% (95% CI, 49.7%-54.3%), a specificity rate of 99.55% (95% CI, 99.52%-99.58%), and a cancer signal origin accuracy rate of 92.5% (95% CI, 90.7%-94.0%). Study-related adverse effects occurred in 0.52% of individuals in the intervention arm and 0.45% of those in the control arm, with no serious study-related AEs reported. An exploratory analysis showed a 25% reduction in cancers diagnosed through emergency presentation in the control (n = 286) vs intervention (n = 213) arms.

In PATHFINDER 2, the false positive rate was 0.36%, and 0.6% of MCED-tested participants underwent an invasive procedure following a positive test result.² Five study-related AEs occurred during diagnostic evaluation, none of which were serious. The median time to diagnostic resolution was 48 days (Q1-Q3, 29-92) for participants with a positive result.

References

1. GRAIL announces FDA advisory committee meeting to review premarket approval application for the Galleri multi-cancer early detection test. News release. GRAIL, Inc. August 7, 2026. Accessed August 11, 2026. https://grail.com/press-releases/grail-announces-fda-advisory-committee-meeting-to-review-premarket-approval-application-for-the-galleri-multi-cancer-early-detection-test/
2. Giridhar KV, McDonnell CH III, Kurbegov D, et al. Safety and performance results from PATHFINDER 2, a registrational study of a multi-cancer early detection (MCED) test in an intended-use population. J Clin Oncol. 2026;44(suppl 17):LBA10509. doi:10.1200/JCO.2026.44.17_suppl.LBA10509
3. Swanton RC, Johnson P, Round T, et al. NHS-Galleri: primary results from a randomised controlled trial to assess the clinical utility of a multi-cancer early detection (MCED) test in population screening. J Clin Oncol. 2026;44(suppl 17):LBA100. doi:10.1200/JCO.2026.44.17_suppl.LBA100