Does Screening With the Galleri Test in the NHS Reduce the Likelihood of a Late-stage Cancer Diagnosis in an Asymptomatic Population? A Randomised Clinical Trial (NHS-Galleri)

A Randomized, Controlled Trial to Assess the Clinical Utility of a Multi-cancer Early Detection (MCED) Test for Population Screening in the United Kingdom (UK) When Added to Standard of Care

The Galleri test is a new test that looks for potential signs of cancer in a blood sample. The test can find many different types of cancer but cannot find all cancers. The trial aims to see if using the Galleri test alongside standard cancer testing in the NHS can help to find cancers at an early stage when they are easier to treat.

The trial has enrolled approximately 140,000 participants who will be actively followed for approximately three years from the date of enrollment.

Study Overview

• Status: Active, not recruiting
• Conditions: Cancer
• Intervention / Treatment: Device: Multi-cancer early detection test (Galleri test)

Detailed Description

This is a prospective, randomized, controlled trial to assess the performance and clinical utility of a multi-cancer early detection test for population screening in the UK when added to standard of care. Participants and the study teams remain blinded throughout the study with the exception of the study nurses returning the results and a small number of staff to enable them to perform administrative duties. Blinding is maintained for participants with the exception of those participants who test positive. Those who test positive will be informed by designated trial staff and will be referred for standard of care investigations and treatment. Trial sponsor employees, the CIs and site staff (unless identified differently in the blinding plan for study conduct needs) will remain blinded throughout the study.

Randomization will be to either the intervention arm, with blood collection and evaluation of the test with consequent investigation and treatment of a positive test through referral to the NHS urgent two week wait pathway, or to the control arm, where blood samples are collected at designated intervals and will be stored for potential future evaluation, but participants do not receive test results and otherwise continue to receive routine NHS care.

Unless diagnosed with cancer, participants in both arms will be asked to return for annual visits at approximately 12 and 24 months. All participants whether test positive, test negative or not tested will be followed for cancer and associated outcomes via NHS dataset linkages.

• Study Type: Interventional
• Enrollment (Actual): 142318
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Macclesfield, United Kingdom
    • EMS Healthcare Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Participants must be at 50-77 years of age, inclusive, at the time of data extraction from NHS datasets or GP records used to identify potential participants; and
2. Capable of giving signed and legally effective informed consent, which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and in this protocol. Consent provided by a legally authorised representative is not permitted in this protocol.

Exclusion Criteria:

1. Previous or current participation in another GRAIL-sponsored study.
2. Personal history of invasive cancer or haematologic malignancy, diagnosed within the three years prior to expected enrolment date. Note: Individuals with a diagnosis of non-melanoma skin cancer and prostate cancer patients whose only treatment is active surveillance are NOT excluded
3. Definitive treatment for invasive cancer or haematologic malignancy within the 3 years prior to expected enrolment date, including adjuvant hormone therapy for cancer (e.g. for breast or prostate cancer).
4. Currently taking demethylating or cytotoxic agents for any condition.
5. Undergoing current investigation for suspected cancer, defined as having been referred to a two week wait clinic or undergoing investigations at an RDC or other clinic with a stated suspicion of cancer.
6. Currently on a palliative care pathway.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Interventional; Blood collection and multi-cancer early detection testing with return of positive test results.	Device: Multi-cancer early detection test (Galleri test); Blood collection and multi cancer early detection testing with return of positive test results.; Other Names: Galleri test
No Intervention: Control; Blood collection only.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of stage III and IV cancers diagnosed in the intervention arm as compared with the control arm	using a fixed-sequence statistical strategy as below: first, evaluate for a statistically significant difference in a prespecified group of primary cancer types: lung, head & neck, colorectal, pancreas, myeloma/plasma cell neoplasm, liver/bile duct, stomach, oesophagus, anus, lymphoma, ovary, and bladder.; if a statistically significant reduction in absolute numbers is found, continue by evaluating for a difference in all cancer types excluding prostate cancer.; If the above evaluations are both significant, evaluate for a difference in all cancer types.	3-4 years after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of advanced cancers (stage III and IV cancers or one that results in a cancer-specific death) diagnosed in the intervention arm as compared with the control arm.		3-4 years after randomization
incidence of stage IV cancers diagnosed in the intervention arm as compared with the control arm	sequentially: for a prespecified group of 12 cancer types: lung, head & neck, colorectal, pancreas, myeloma/plasma cell neoplasm, liver/bile duct, stomach, esophagus, anus, lymphoma, ovary, and bladder.; for all cancer types excluding prostate cancer.; for all cancer types.	1 year after randomization
incidence of all cancers diagnosed in the intervention arm as compared with the control arm		1 year after randomization
incidence of stage IV cancers following the second blood draw and 12 months of follow-up, with prevalent cases excluded		2 years after randomization
incidence of stage IV cancers diagnosed in the intervention arm as compared with the control arm.	sequentially: for a prespecified group of 12 cancer types: lung, head & neck, colorectal, pancreas, myeloma/plasma cell neoplasm, liver/bile duct, stomach, esophagus, anus, lymphoma, ovary, and bladder.; for all cancer types excluding prostate cancer.; for all cancer types.	3-4 years after randomization
modelled cancer mortality at 7 years post-randomization based on cancers diagnosed within 3-4 years after randomization in the intervention arm as compared with the control arm.		3-4 years after randomization
stage distribution by cancer type for the two arms.		3-4 years after randomization
incidence of stage III and IV cancers excluding breast, cervical, and colorectal diagnosed in the intervention arm as compared with the control arm.		3-4 years after randomization
incidence of stage III/ IV cancers following the third blood draw.		3-4 years after randomization
overdiagnosis by comparing the cumulative number of cancers diagnosed within 3-4 years of randomisation in individuals with a positive baseline test (evaluated retrospectively in the control arm) between arms.		3-4 years after randomization
cancer-specific mortality in the intervention arm as compared with the control arm.	specifically: nested cancer-specific mortality up to 5 years after randomization.; cancer-specific mortality (up to 5 years and) up to 8 years after randomization.	up to 8 years after randomization
proportion of stage I and II cancers in the intervention arm as compared with the control arm in the third screening round.		3-4 years after randomization
test performance (sensitivity, specificity, positive predictive value, negative predictive value) and cancer signal origin accuracy) in the intervention arm.		Up to 3 years after randomization
participant-reported psychological impact including anxiety, at various timepoints in all test positive cases.		Up to 1 year after randomization
number and type of invasive procedures performed, and complications and deaths associated with follow-up diagnostic procedures in all test positive cases.		Up to 3 years after randomization
radiation exposure by participants associated with follow-up diagnostic procedures following a positive MCED test result.		Up to 3 years after randomization
use of the MCED test across three annual timepoints on healthcare resource utilization for cancer diagnosis and treatment.		Up to 3 years after randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
healthcare resource utilisation	The data collected may be used to conduct future exploratory economic analyses, and will include: Number and types of medical encounters and cancer-specific diagnostic and treatment procedures, including clinical lab visits, imaging tests, invasive tests, and clinic visits.	Up to 3 years

Collaborators and Investigators

• Sponsor: GRAIL, Inc.
• Collaborators: The Cancer Research UK Cancer Prevention Trials Unit at Queen Mary University of London (CPTU)
• Investigators: Study Director: Harpal Kumar, GRAIL, Inc.

Publications and helpful links

General Publications

• Neal RD, Johnson P, Clarke CA, Hamilton SA, Zhang N, Kumar H, Swanton C, Sasieni P. Cell-Free DNA-Based Multi-Cancer Early Detection Test in an Asymptomatic Screening Population (NHS-Galleri): Design of a Pragmatic, Prospective Randomised Controlled Trial. Cancers (Basel). 2022 Oct 1;14(19):4818. doi: 10.3390/cancers14194818.
• Marlow LAV, Schmeising-Barnes N, Warwick J, Waller J. Psychological Impact of the Galleri test (sIG(n)al): protocol for a longitudinal evaluation of the psychological impact of receiving a cancer signal in the NHS-Galleri trial. BMJ Open. 2023 Jul 21;13(7):e072657. doi: 10.1136/bmjopen-2023-072657.
• Brentnall AR, Mathews C, Beare S, Ching J, Sleeth M, Sasieni P. Dynamic data-enabled stratified sampling for trial invitations with application in NHS-Galleri. Clin Trials. 2023 Aug;20(4):425-433. doi: 10.1177/17407745231167369. Epub 2023 Apr 24.
• Marlow LAV, Schmeising-Barnes N, Waller J. Experience of NHS diagnostic investigation following a multi-cancer early detection (MCED) screening test: qualitative interviews with NHS-Galleri trial participants who had a cancer signal detected. EClinicalMedicine. 2026 Jan 8;91:103733. doi: 10.1016/j.eclinm.2025.103733. eCollection 2026 Jan.
• Swanton C, Bachtiar V, Mathews C, Brentnall AR, Lowenhoff I, Waller J, Bomb M, McPhail S, Pinches H, Smittenaar R, Hiom S, Neal RD, Sasieni P. NHS-Galleri trial: Enriched enrolment approaches and sociodemographic characteristics of enrolled participants. Clin Trials. 2025 Apr;22(2):227-238. doi: 10.1177/17407745241302477. Epub 2025 Jan 25.
• Smittenaar R, Quaife SL, von Wagner C, Higgins T, Hubbell E, Lee L. Impact of screening participation on modelled mortality benefits of a multi-cancer early detection test by socioeconomic group in England. J Epidemiol Community Health. 2024 May 9;78(6):345-353. doi: 10.1136/jech-2023-220834.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): July 1, 2030

Study Registration Dates

• First Submitted: October 28, 2022
• First Submitted That Met QC Criteria: November 3, 2022
• First Posted (Actual): November 10, 2022

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: cancer screening; multi-cancer early detection; circulating cell-free tumor DNA; MCED
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: GRAIL-009; ISRCTN91431511 (Registry Identifier: ISRCTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes