FDA MCGP Panel Votes in Favor of the Galleri Multicancer Early Detection Test

The FDA’s Molecular and Clinical Genetics Panel of the Medical Devices (MCGP) advisory committee convened to vote on 3 questions regarding the Galleri multicancer early detection test.¹

The 3 questions that the panel voted on were:

1. Is there reasonable assurance that Galleri is safe for use in patients who meet the criteria specified in the proposed indication?
   1. The panel voted 10 to 0 in favor.
2. Is there reasonable assurance that Galleri is effective for use in patients who meet the criteria specified in the proposed indication?
   1. The panel voted 6 to 4 in favor.
3. Do the benefits of Galleri outweigh the risk for use in patients who meet the criteria specified in the proposed indication?
   1. The panel voted 7 to 2 in favor, with 1 abstention.

The executive summary released by the FDA prior to the meeting revealed proposed indications for the test by the developer, as well as potential precautions and limitations of the device.² The developer of Galleri, GRAIL, has proposed that the test should be indicated for the screening for early detection of multiple types of cancer, in adults 50 years or older. They also proposed an indication for the prediction of Cancer Signal Origin in individuals with a cancer signal detected test result. Among the precautions and limitations were that the Galleri test is not a replacement for existing recommended single-cancer screening tests or diagnostic modalities for cancer, that a result of no cancer signal detected does not rule out the presence of cancer, and that a result of cancer signal detected still requires diagnostic testing with a medically established procedure to confirm the presence of cancer. It was also noted that the Galleri test may also produce false positive or false negative results, and that the benefits and risks of programmatic cancer screening with Galleri are still being studied.

What is Galleri?

Galleri is a next-generation sequencing-based cancer screening test that identifies DNA methylation patterns on cell-free DNA (cfDNA) in plasma from patients aged 50 years or older. For the test, whole blood is collected prior to plasma isolation, cfDNA extraction, and bisulfite conversion of the extracted cfDNA. The test has 3 classes of reportable results:

The cancer signal classifier: Determines the result as either cancer signal detected (positive) or no cancer signal detected (negative).

1. The cancer signal origin classifier: Predicts the likely anatomic location of the detected signal. Only returned in the event of a positive result.
2. The cancer signal origin – supplemental classifier: Predicts cancer biology, such as histologic type and cellular lineage of the origin. Only returned in the event of a positive result.

The Galleri test had been granted breakthrough device designation in August 2018, and more recently, has been granted 2 investigational device exemptions. The first came in September 2021 and was based on the PATHFINDER 2 study (NCT05155605), and the second came in November 2022 and was based on the NHS-Galleri trial (NCT05611632).

How effective is the Galleri test?

NHS Galleri

The New England Journal of Medicine published results from NHS-Galleri on September 22, 2026, the day before the MCGP meeting.³ NHS-Galleri evaluated the incidence rate of detecting cancer with the Galleri multicancer early detection testing plus usual care vs usual care alone. A lower incidence rate of stage III or IV cancers across 12 prespecified cancers was not observed following 3 screening rounds in the interventional group.

Among the 142,250 patients who underwent randomization, 71,034 were clinically eligible in the intervention group and 71,033 in control group. Of these, 3637 patients in the intervention group and 3400 in the control group received a diagnosis of a routinely staged cancer; of those, 1421 and 1298 patients, respectively, were diagnosed with one of the 12 prespecified cancers.

After 3 rounds of screening, 706 and 688 patients, respectively, were diagnosed with stage III or IV cancer among the 12 prespecified cancer types, correlating with an incidence rate per 100,000 person-years of 300.5 (95% CI, 278.7-323.5) in the intervention group and 292.5 (95% CI, 271.0-315.1) in the control group. No significant difference in the incidence rate for stage III or IV cancer was observed between the 2 groups (incidence rate ratio, 1.03; 95% CI, 0.92-1.15; P = .63). A post hoc analysis revealed that the overall result was driven by a higher incidence rate of stage III or IV cancers in the intervention group in the first round of screening (incidence rate ratio, 1.19; 95% CI, 0.98-1.43). Contrasting this, in the second and third rounds of screening, the incidence rate ratios were 0.95 (95% CI, 0.77-1.17) and 0.88 (95% CI, 0.73-1.07), respectively.

For patients with the 12 prespecified cancers, the incidence rate of stage IV cancer per 100,000 person-years was 145.2 (95% CI, 130.2-161.4) in the intervention group and 168.5 (95% CI, 152.3-185.9) in the control group, correlating with an incidence rate ratio of 0.86 (95% CI, 0.74-1.00).

In a post hoc analysis of early-stage diagnoses across the 12 prespecified cancers after 3 screening rounds, stage I or II cancers were identified in 647 patients in the intervention group and 559 in the control group (relative risk, 1.16; 95% CI, 1.03-1.30); stage I, II, and III cancers were reported in 1007 and 846 patients, respectively (relative risk, 1.19; 95% CI, 1.09-1.30). Results were similar for patients with all routinely stages cancer types.

Regarding safety, adverse events (AEs) that were trial related, device related, or both occurred in 371 patients (0.52%) in the intervention group and 321 (0.45%) in the control group. None were considered serious. Device-related AEs occurred in 27 patients (0.04%) in the intervention group. Across both groups, the most common trial-related AEs were vessel bruises at the puncture site, syncope, dizziness, vessel hematomas at the puncture site, and anxiety.

Patients were eligible for the trial if they were 50 to 77 years old, did not have a cancer diagnosis or treatment within 3 years prior to enrollment, and were not being assessed for possible cancer. The 12 prespecified types of cancer were lung, head and neck, colon or rectum, pancreas, multiple myeloma or plasma cell neoplasm, liver or bile duct, stomach, esophagus, anus, lymphoma, ovary, and bladder, which account for more than 60% of cancer deaths.

PATHFINDER 2

Similar to NHS-Galleri, results from the PATHFINDER 2 study were published on September 22, 2026, in Nature Medicine.⁴ PATHFINDER 2 evaluated the Galleri test in patients 50 years or older without clinical suspicion of cancer. A total of 32,007 patients enrolled in the trial completed their 12-month cancer assessment. Of them, 173 patients had true-positive test results, correlating to a detection rate of 0.54%, a positive predictive value (PPV) of 60.3%), and a negative predictive value (NPV) of 99.2%. The specificity was 99.64%, and the 12-month episode sensitivity was 39.3% for all cancers and 69.8% for a prespecified subgroup of 12 cancers.

A total of 267 patients had false-negative test results, of which 163 had United States Preventive Services Task Force (USPSTF) grade A/B/C-recommended screening.

Regarding safety, of all 35,335 patients included in the safety analysis set, the proportion of patients with an invasive procedure after a positive test result was 0.6% (n = 213/35,335), with 0.01 invasive procedures per patient. Notably, almost twice as many patients with true-positive results experienced invasive procedures during targeted evaluation compared with those who had false-positive results (88.6% vs 46.3%, respectively). A total of 114 patients received a false-positive result, which is 59 fewer than the 173 true-positives.There were 4 patients with a false-positive result who experienced a surgical procedure due to necessity to clear suspicion of cancer; in all cases, benign neoplasms were discovered.

Patient-reported anxiety increased temporarily for patients with true-positive test results, though returned to baseline by 12 months. For those with either false-positive or false-negative results, anxiety did not increase.

Eligible patients in the trial were 50 years or older and capable of giving signed and legally effective informed consent, and were not undergoing or referred for diagnostic evaluation due to clinical suspicion of cancer.

References

1. CDRH: molecular and clinical genetics panel of the medical devices advisory committee (MDAC). YouTube. September 23, 2026. Accessed September 23, 2026. https://tinyurl.com/2wmec9b4
2. FDA executive summary: Prepared for the September 23, 2026 meeting of the Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee. FDA. Accessed September 23, 2026. https://tinyurl.com/4p77anmp
3. Sasieni P, Johnson P, Round T, et al. Effect of screening with multicancer early-detection test on late-stage cancer diagnosis. N Engl J Med. Published September 22, 2026. doi:10.1056/NEJMoa2505723
4. Nabavizadeh N, McDonnel C, Kurbegov D, et al. Performance and safety of a multi-cancer early detection test: the PATHFINDER 2 study. Nat Med. Published online September 22, 2026. doi:10.1038/s41591-026-04618-w