What was the committee asked to consider? 

On September 23, the U.S. Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH) convened the Molecular and Clinical Genetics Panel (MCGP) of the Medical Devices Advisory Committee to consider data supporting a premarket approval application (PMA) for GRAIL’s Galleri test. Galleri is a qualitative, next-generation sequencing (NGS)-based in vitro diagnostic (IVD) test intended to detect cancer-specific methylation patterns in cell-free DNA isolated from peripheral whole blood. The proposed indication is for screening for the early detection of multiple types of cancer in adults aged 50 and older. Galleri returns a positive (“Cancer Signal Detected”) or negative (“No Cancer Signal Detected”) result. A positive result also includes a “Cancer Signal Origin” that predicts the likely location of the detected cancer. The proposed indication specifies that a negative result does not rule out the presence of cancer, and individuals should continue with regular guideline-recommended single-cancer screening tests. 

This meeting was convened after GRAIL submitted a PMA to the FDA for Galleri in January 2026. Galleri was designated as a Breakthrough Device by the FDA in 2018.  

The FDA asked the committee to vote on 3 key questions: 

• Question 1: Is there reasonable assurance that Galleri is safe for patients who meet the criteria specified in the proposed indication? 
• Question 2: Is there reasonable assurance that Galleri is effective for use in patients who meet the criteria specified in the proposed indication? 
• Question 3: Do the benefits of Galleri outweigh the risks for use in patients who meet the criteria specified in the proposed indication? 

Why does this matter for patients and diagnostics development? 

Unmet Need 

Early detection is critical to cancer control, as it can expand treatment options, including the potential for curative-intent therapy, and is generally associated with better outcomes. Established cancer screening programs can detect asymptomatic disease in certain cancers (e.g., breast, colorectal, cervical, prostate, and lung in high-risk smokers), but effective screening tools do not exist for most cancers. Many cancers, especially those without established screening programs, are often diagnosed at later stages once a patient becomes symptomatic, which frequently leads to worse outcomes than cancers detected earlier. The Galleri test would provide a new tool for detecting cancers, particularly those for which established screening methods do not exist, with the potential to identify some cancers at a stage when curative-intent treatment remains possible. Patients and providers who caught aggressive cancers early using the Galleri test shared their stories during the public hearing portion of the meeting—their experiences highlighted how transformative early detection can be for patient outcomes. The Galleri test also enables detection of multiple cancers at once through a single blood test, providing an opportunity to maximize population-level cancer screening and detection.  

There are currently no FDA-authorized devices indicated for the screening of multiple types of cancer. Current challenges in Multi-Cancer Early Detection (MCED) tests lie in their performance and the clinical decision-making informed by their results. False positive results lead to unnecessary workups and psychological distress for patients, while false negative results may provide false reassurance and affect adherence to other recommended cancer screening. To minimize potential harms associated with incorrect or misinterpreted results, MCED tests must be carefully evaluated and validated, and guidelines for their use must be clear. 

What was discussed? 

Sponsor Perspective 

GRAIL’s presentation focused on the unmet need for cancer screening options, device development and validation, and performance data from two related trials: PATHFINDER2 and NHS-Galleri. Galleri’s clinical performance was evaluated retrospectively using stored specimens from prospective trials conducted with their previous MCED-V2 assay. Therefore, the safety data presented reflected that of MCED-V2, while performance estimates of Galleri were a result of the retrospective testing of those specimens with the final Galleri assay. 

In both studies, Galleri showed high positive predictive values (PPVs) (PATHFINDER2 PPV = 77.0%, NHS-Galleri PPV = 66.2%) and high negative predictive values (NPVs) (PATHFINDER2 NPV = 99.07%, NHS-Galleri NPV = 98.89%). PPV refers to the probability that a person with a positive result has cancer, and NPV refers to the probability that a person with a negative result does not have cancer. They also presented low false positive rates (PATHFINDER2 = 0.15%, NHS-Galleri = 0.26%), indicating the test rarely produced a positive result in individuals who did not have cancer. Of the patients that received a positive cancer signal detection result, the test accurately determined the anatomical site of the cancer through its cancer signal origin (CSO) and cancer signal origin supplement (CSO-S) metrics (PATHFINDER2: CSO = 94.3%; NHS-Galleri: CSO = 91.9%, CSO-S = 93.1%). GRAIL also presented data supporting the safety of the test (associated with MCED-V2, not the Galleri device seeking PMA), listing very few adverse events, most of which were associated with diagnostic follow-up rather than the administration of the test itself. 

FDA Perspective 

The FDA’s presentation focused on the benefit and risk considerations of the Galleri test. The FDA argued that while the safety of these tests (assessed by MCED-V2 and not directly by Galleri) was not of major concern, there are remaining questions about the effectiveness of the test in early-stage cancer and the episode sensitivity of the test. The proposed indication for Galleri makes claims about its ability to detect cancers early. However, Galleri detected 13.6–21.4% of Stage I cancer but performed better in detecting late-stage cancer (rising to 60.0% for Stage IV cancer). 

For the PMA submission, non-cancer status was determined after approximately 12 months of follow-up time. Thus, the sensitivity of Galleri is reported as 12-month episode sensitivity, which is defined as the test’s ability to identify cancer diagnosed during a 12-month follow-up period after testing (i.e., a 12-month episode duration). The episode sensitivity for both studies showed that Galleri only detected one-third of the cancers diagnosed within that follow-up period (PATHFINDER2 = 35.0%, NHS-Galleri = 31.6%). 

The FDA highlighted two areas to discuss as part of its broader benefit-risk assessment. The first related to false negatives, that even with its intent of being an adjunct test to current screening guidelines, patients may find false reassurance in a false negative result and forgo guideline recommended screening if Galleri is interpreted as a replacement rather than an adjunct. The second related to false positives, exposing patients to unnecessary diagnostic procedures and emotional stress.

Panel Discussion 

Panelists considered the clinical significance of test performance, including across stages and cancer types, whether the data support the proposed use for “early” detection of multiple types of cancer, potential risks and mitigation strategies, appropriate communication and guidelines to support provider and patient decision-making, and the types of information that should be collected in potential post-approval studies. Panelists questioned the added value of the test for cancers with existing recommended screening but recognized its promise for cancers that lack recommended screening methods. The panel discussed whether the wording “early detection” included in the proposed indication should be used since test sensitivity was low for early-stage cancer, and “early” holds different meanings across cancer types. Panelists were also concerned about the potential impacts of false negative and false positive results, including the risk of a false negative leading patients to skip existing recommended screenings, unnecessary workups from false positive results, especially in older patients, and potential overuse of the test related to consumer advertising. The panel advocated for plain-language labeling and physician education to ensure proper test use and recommended post-approval studies collect information to further characterize the test’s impacts on clinical outcomes such as mortality, the impacts of false results on screening adherence, and performance in certain subgroups.

What are the outcomes and implications of this meeting? 

The committee voted in favor of Galleri’s safety (10 Yes, 0 No), effectiveness (6 Yes, 4 No), and its benefits outweighing its risks (7 Yes, 2 No, 1 Abstain). Support was largely driven by the need for screening methods in cancer types without an existing screening approach, which this test could provide. Members of the committee reiterated that the test should be used in adjunct to current recommended screening guidelines and that post-market surveillance will be important to increase confidence in its effectiveness by providing clinical outcomes data. Discussion also highlighted the lack of an established definition of “early” stage cancer, and whether the proposed indication and labeling may need to be adjusted to address differences in the effectiveness of this test by patient age group and cancer stage. More broadly, the meeting highlighted an emerging challenge for MCED development: how to evaluate screening tests that may offer new opportunities to detect cancers with no established screening methods, while demonstrating heterogeneous sensitivity across cancer types and stages and before evidence of downstream clinical benefit is mature.

MCGP meeting materials and recording are available here: September 23, 2026: Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee Meeting Announcement