TEST:

Galleri Test

"GRAIL, Inc...announced early results from the REFLECTION study, which aims to understand the real-world experience of the Galleri® multi-cancer early detection (MCED) test in routine clinical settings. The Galleri test is recommended for adults with an elevated risk for cancer, such as those age 50 or older. In this study, a diverse population of veterans from U.S. Department of Veterans Affairs (VA) sites with toxic exposure but with no symptoms suggestive of cancer were included in study enrollment. Initial results showed that among study participants, the veteran cohort had a cancer signal detection rate consistent with other populations that have received the MCED test. The findings were presented during a presentation at the 2024 Early Detection of Cancer Conference (EDCC)."

We previously expressed concerns about the sensitivity and specificity of the Galleri test. In this Perspective, we revisit the hyped technology, and we provide new suggestions on the use of this test.

P=N/A; Not yet recruiting --> Recruiting

P=N/A, N=250, Enrolling by invitation, GRAIL, Inc.

Overview of current liquid biopsy technologies 2. Discuss clinical utility and applications of cfDNA-based tests in Hematologic Malignancies.

P=NA | N=NA | "GRAIL, Inc...announced that detailed findings of the performance of its Galleri multi-cancer early detection (MCED) test in prostate cancer were published in JCO Precision Oncology....Results from this analysis showed that of the prostate cancers that were detected by the MCED test, most were clinically significant (93% were intermediate or high grade and 67% were stage III or IV). For detected prostate cancers, the cancer signal of origin (CSO) prediction accuracy was > 90%. Detectability for stage I and II cancers were 4.2% across both studies combined, which is expected with low shedding prostate cancer tumor fraction and is consistent with cfDNA literature in prostate cancer. Test sensitivity of prostate cancer for all stages was 11.2% in substudy CCGA-3."

P=N/A; N=1500; Not yet recruiting; Sponsor:Dana-Farber Cancer Institute

"GRAIL, Inc...today announced that the first participant has been enrolled in the REACH/Galleri-Medicare study at Community Health Network, a leading integrated healthcare system in central Indiana with more than 200 sites of care....The Real-world Evidence to Advance Multi-Cancer Early Detection Health Equity (REACH/Galleri-Medicare) study is a first-of-its-kind real-world evidence study designed to further evaluate the clinical impact of the Galleri multi-cancer early detection (MCED) test in Medicare beneficiaries."

"GRAIL, Inc...today provided an update on the PATHFINDER 2 and NHS-Galleri registrational clinical trials evaluating the Galleri multi-cancer early detection (MCED) test. GRAIL has completed the PATHFINDER 2 study's planned enrollment of more than 35,000 participants who are eligible for guideline-recommended cancer screening at more than 30 healthcare institutions in North America. In addition, GRAIL has completed the third and final round of study visits for the NHS-Galleri trial, which enrolled more than 140,000 participants....'We look forward to seeing results from the first 25,000 individuals enrolled in the PATHFINDER 2 study in the second half of 2025 and final results from the NHS-Galleri trial in 2026.'"

P=N/A; N=1000; Not yet recruiting; Sponsor:Dana-Farber Cancer Institute

"The UK National Health Service said...that it will not be accelerating the implementation of Grail's Galleri multi-cancer early detection test, following a review of data from the first year of their clinical study."

"GRAIL, LLC...will present new data on the clinical utility of its Methylation Platform across the cancer continuum, and the impact of multi-cancer early detection (MCED) testing in guiding diagnostic evaluation at the American Association for Cancer Research (AACR) Annual Meeting in San Diego, Calif., April 5-10, 2024....Demonstrating the first real-world evaluation of repeat MCED / Galleri testing showing the potential value of adding repeat MCED screening. The timeframe for repeat testing occurred 10-18 months from initial MCED testing. Exhibiting 4-year overall survival follow-up demonstrating the prognostic significance of detecting cancer with a methylation-based cfDNA platform like Galleri."

The performances of SeekInCare in both retrospective and prospective studies demonstrate that SeekInCare is an effective blood-based MCED test with similar performance as Grail's Galleri test, which paves the way for clinical utility as a cancer screening test in average-risk populations.

"Getlabs...announced that it will be adding GRAIL's Galleri^Ⓡ multi-cancer early detection test to its list of test offerings. Getlabs will facilitate the sample collection process for the Galleri test by bringing the convenience of at-home blood draws to patients, eliminating the need for visits to clinics and reducing barriers to testing."

"Curative Insurance Company...and GRAIL...announced the availability of Galleri®, a multi-cancer early detection (MCED) screening test to eligible insurance plan members. The Galleri test will be available to all members, across all plan types, who are over the age of 50 and to all other members with risk factors for developing cancer. The Galleri test is part of the expansive list of benefit offerings available for $0 copay and $0 deductible* on Curative's health insurance plan."

"GRAIL, LLC...and BeniComp...announced the availability of Galleri®, a multi-cancer early detection (MCED) screening test, to eligible patients initially through BeniComp Select members. This partnership underscores BeniComp’s commitment to proactive and preventive health management, enabling an even broader reach of their transformative health insurance products."

"GRAIL, LLC...announced that it will initiate Real-world Evidence to Advance Multi-Cancer Early Detection Health Equity (REACH/Galleri-Medicare study) following the U.S. Food and Drug Administration’s (FDA) approval of GRAIL’s Investigational Device Exemption (IDE) application and the Centers for Medicare and Medicaid Services’ (CMS) approval for Medicare coverage of the study. With age being the most significant risk factor for cancer, Medicare beneficiaries face the highest unmet need for early cancer detection."

"To demonstrate clinical utility in an asymptomatic population, these tests must be shown to reduce cancer mortality without causing excessive overdiagnosis in a large randomized prospective randomized trial. Such trials are currently ongoing for Galleri and CancerSEEK."

In this pilot study, we observed that MCED testing was effective in detecting Stage II, III, and IV TNBC across SRE. These findings, in combination with the association of estimated ctDNA abundance with cancer stage but not patient SRE, provide hypothesis-generating evidence that analysis of methylation signals from across the genome can provide meaningful TNBC screening/detection information, independent of self-reported race/ethnicity. Table 1.

Findings from two large validation studies and RWE demonstrate that Galleri promises to be a state of the art molecular tool that detects a shared cancer signal and is able to identify a large variety of histopathologic entities of lymphoid and plasmacytic origin, which currently have no other standard of care screening regimen. This tool may lead to better treatment outcomes and decreased mortality saving lives through the early detection of these previously unscreened cancers.

"...Sarah Cannon Cancer Institute, part of HCA Healthcare, and GRAIL, LLC...announced a strategic collaboration to advance comprehensive cancer care through early detection...GRAIL’s Galleri® multi-cancer early detection (MCED) test will be available to patients who meet screening criteria at select HCA Healthcare physician practices."

"GRAIL, LLC...announced that detailed findings from the PATHFINDER study of its multi-cancer early detection (MCED) blood test have been published in The Lancet. The study, conducted in 6,662 adults over the age of 50 without symptoms suggestive of cancer, demonstrated that an earlier version of GRAIL’s MCED test identified many cancer types that do not currently have recommended screening tests, enabled targeted cancer diagnostic evaluations, and supported diagnostic resolution for the majority of participants in less than three months."

"Point32Health...GRAIL...announced the expansion of their pilot to offer GRAIL’s groundbreaking Galleri^® multi-cancer early detection screening test. The pilot includes members meeting eligibility requirements whose primary care provider (PCP) is a Mass General Brigham affiliated provider and who are covered under a Harvard Pilgrim Health Care or Tufts Health Plan employer-sponsored plan or a Harvard Pilgrim Health Care Massachusetts Connector plan."

"Whitman-Walker Institute...Cancer Support Community (CSC)...and GRAIL, LLC...announced a research collaboration aimed at advancing health equity in cancer screening and care with GalleriⓇ, a multi-cancer early detection (MCED) test, in diverse patient populations...The Implementation and Navigation of Cancer Liquid biopsy to Understand Diverse Patient Experiences (INCLUDE) study will evaluate established community outreach strategies intended to build awareness and increase early cancer screening."

P=N/A; A separate consent form will be required for interview. Results will be disseminated via peer-reviewed publication and conference presentations.

"GRAIL, LLC...announced data evaluating the Galleri® multi-cancer early detection (MCED) test’s ability to detect a cancer signal and predict the cancer signal origin (CSO) in asymptomatic individuals in the real-world setting...Positive Galleri results with a CSO prediction were associated with a diagnosis of invasive cancer across multiple cancer types, including stage I and II cancers. The findings were presented during a poster discussion session at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting."

"GRAIL, LLC...announced results from a retrospective analysis of the interventional PATHFINDER study to assess whether diagnostic evaluations of individuals who received a cancer signal detected (CSD) result with the Galleri® multi-cancer early detection (MCED) test were appropriately directed by the test’s cancer signal origin (CSO) predictions. The findings demonstrated that in the majority of cases (78%), the test’s CSO-directed initial diagnostic evaluation led to a diagnostic resolution. The findings were presented during a poster discussion session at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting."

"GRAIL, LLC...will present new data evaluating the use and potential of its methylation-based multi-cancer early detection (MCED) platform at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, June 2-6. Presentations include interim results from SYMPLIFY, the first large-scale prospective study to evaluate GRAIL’s MCED test in symptomatic patients referred for cancer suspicion, as well as Galleri® real-world clinical surveillance data and subset analyses from the PATHFINDER clinical implementation study. An evaluation of Galleri implementation using a centralized model within Mercy’s multi-state health system will also be presented."

P=N/A; Not yet recruiting --> Recruiting | Initiation date: Oct 2023 --> May 2023

In sum, Galleri, as a population-based cancer screening test, is not economically affordable, not ethically equitable, and only marginally medically beneficial.

RW experience with the MCED test was consistent with previous large-scale clinical studies with an average CSDR of 1.0%, which increased with age. The test detected a CS and predicted CSO across multiple cancers, including early-stage cancers and cancers w/o recommended screening. This indicates that the MCED test can reliably detect a CS, which is essential to support population screening.

This model allowed for efficient time to diagnosis and tx or triage of eligible-risk pts using an MCED test and is an example of how a healthcare system can incorporate and scale the implementation of the MCED test into clinical practice.

"FirstHealth of the Carolinas, Inc...and GRAIL, LLC...announced the availability of Galleri®, a multi-cancer early detection (MCED) screening test to eligible patients initially through FirstHealth’s Concierge Medicine Clinic in Southern Pines. FirstHealth will be the first health system in North Carolina to offer the Galleri MCED test to those at an elevated risk of cancer, including those aged 50 or older, as part of its comprehensive cancer screening and care. Additional primary care clinics will offer the test in the coming months."

"GRAIL, LLC...will present new data showcasing the performance of its methylation platform to detect cancer across the early- and post-diagnosis settings at the American Association for Cancer Research (AACR) Annual Meeting in Orlando, April 14-19, 2023."

P=N/A; Initiation date: Jan 2023 --> Oct 2023

"Providence...and GRAIL, LLC...today announced the expansion of their partnership to offer multi-cancer early detection screening as part of clinical care to eligible individuals across the entire Providence health system....Through the partnership, eligible patients at Providence’s 52 hospitals and 900 clinics across seven states will have access to GRAIL’s Galleri® multi-cancer early detection (MCED) test, as part of a comprehensive range of health services."

"John Hancock, a unit of Manulife (NYSE: MFC), announced it will expand access to GRAIL’s Galleri® multi-cancer early detection test to eligible life insurance customers participating in the John Hancock Vitality PLUS program, a significant milestone in John Hancock’s ongoing efforts to help customers live longer, healthier, better lives. The expanded access comes after John Hancock became the first life insurance carrier to make the breakthrough screening technology available to a pilot group of customers in September 2022."

J.P. Morgan 41st Annual Healthcare Conference Presentation

J.P. Morgan 41st Annual Healthcare Conference Presentation

"Point32Health...and GRAIL...announced the expansion of their pilot to offer GRAIL’s groundbreaking Galleri® multi-cancer early detection blood test to Harvard Pilgrim members at no cost who purchase their insurance on the Maine Health Insurance Marketplace. This expansion is the second phase of a pilot focused on collecting real-world evidence to assess the impact of the Galleri test on health care resource utilization and patient-reported outcomes."

CRC screening with LB alone or with LB in conjunction with colonoscopy among nonadherent patients is not cost-effective in the US context. At this time, LB is unable to detect pre-cancerous colon polyps, which may limit its effectiveness as a CRC screening strategy. >

"GRAIL, LLC...announced findings from a fundamental substudy of the Circulating Cell-free Genome Atlas (CCGA; NCT02889978) study, demonstrating that methylation had the most promising combination of cancer detection and prediction of cancer signal origin when compared with other evaluated approaches. This is the first rigorous and systematic comparison of various genomic measures from circulating cell-free DNA (cfDNA) for multi-cancer early detection (MCED) testing, and the largest comprehensive genome-wide comparison of cfDNA approaches. Findings were published online in Cancer Cell in a manuscript titled 'Evaluation of Cell-Free DNA Approaches for Multi-Cancer Early Detection.'"