GRAIL has had a relatively short but fiery life in the hyper-competitive arena of early cancer detection. But the company has been rather quiet until recently. And for good reason. The latest news from the company could silence their naysayers and show that they were doing the right thing from the get-go.
As a journalist and four-time cancer survivor, I’ve followed Grail closely since they were just coming out of the box, but what we are seeing now is potentially a much more powerful cancer blood test.
GRAIL, whose mission is to detect cancer early when it can be cured, announced that positive performance and safety results from its registrational PATHFINDER 2 study was presented at the European Society for Medical Oncology (ESMO) Congress 2025.
PATHFINDER 2 evaluated the safety and performance of the Galleri® multi-cancer early detection (MCED) test when used alongside standard-of-care cancer screenings.
The largest interventional study of an MCED test in the United States to date, the prospective PATHFINDER 2 study includes 35,878 enrolled participants across the United States and Canada in a broad, intended-use population of adults aged 50 and older with no clinical suspicion of cancer.
Results were presented from a pre-specified analysis of the first 25,578 participants with at least 12 months of follow-up as of Dec. 31, 2024.
Of these, 23,161 were analyzable for performance and 25,114 were analyzable for safety.
“Cancer is the second leading cause of death worldwide, but most deadly cancers are found too late. Adding Galleri to recommended screening for breast, cervical, colorectal, and lung cancers in PATHFINDER 2 yielded a more than seven-fold increase in the cancer detection rate, and more than half of the Galleri detected new cancers were found in early stages, when cancers are more treatable and potentially even curable.
“Galleri’s ability to accurately predict where in the body the cancer signal comes from also helps to guide a more efficient diagnostic workup,” said Josh Ofman, MD, MSHS, President at GRAIL.
“These results are extremely compelling as approximately three-quarters of the Galleri-detected cancers do not have recommended screening tests today. Galleri is the only MCED test available that has been validated in an interventional trial in the screening population and could transform how we deliver cancer screening at a population level.”
Finding More Cancers Earlier By Adding the Galleri Test
Data from the performance analyzable cohort of 23,161 participants with 12 months of follow-up found that adding Galleri to recommended screenings for breast, cervical, colorectal, and lung cancers (USPSTF A and B recommendations) led to a more than seven-fold increase in the number of cancers found within a year.
Galleri detected approximately three times as many cancers when added to standard-of-care screening for breast, cervical, colorectal, lung, and prostate cancers (USPSTF A, B, and C recommendations).
Approximately three-quarters of the cancers detected by Galleri do not have standard of care screening options.
More than half (53.5%) of the new cancers detected by Galleri were stage I or II and more than two-thirds (69.3%) were detected at stages I-III.
“Cancer screening saves lives, but we routinely screen for just four or five cancer types in the United States today and approximately 70% of cancer deaths come from cancers that do not have standard-of-care screening and are typically caught too late,” said Nima Nabavizadeh, MD, Associate Professor of Radiation Medicine at Oregon Health & Science University.
“Data from PATHFINDER 2 show that Galleri could fundamentally change our approach to cancer screening, helping to detect many types of cancer earlier, when the chance of successful treatment or even cure are the greatest.”
High Performance and Low Risk of False Alarm
The Galleri test detected a cancer signal in 216 participants (cancer signal detection rate of 0.93%), and of those, cancer was diagnosed in 133 participants (cancer detection rate of 0.57%).
The likelihood of receiving a cancer diagnosis following a positive test result (positive predictive value) was 61.6%, substantially higher than in the previous PATHFINDER study of Galleri.
Since PATHFINDER 2 is a prospective clinical trial where the cancer status of participants is unknown at the outset, episode sensitivity – the ability to detect cancer that could be confirmed within 12 months after the blood draw – is a performance measure of the study.
Galleri demonstrated strong performance, with 73.7% episode sensitivity for the 12 cancers responsible for two-thirds of cancer deaths in the U.S. For all cancers, episode sensitivity was 40.4%. Specificity was 99.6%, translating to a false positive rate of only 0.4%.
“Any multi-cancer early detection test used for population screening should aim to detect as many aggressive cancers as possible before symptoms arise and maximize the likelihood that a positive test result is actually cancer. The PATHFINDER 2 results demonstrate that the Galleri test is doing just that, increasing the number of cancers detected more than seven-fold when added to recommended screening for breast, cervical, colorectal, and lung cancers, and with a very low false positive rate,” said Ofman.
“What’s especially promising is that Galleri showed strong sensitivity at detecting many of the cancers responsible for the majority of cancer deaths, which we believe provides clinicians with a clinically valuable and validated screening tool.”
High Accuracy of Cancer Signal Origin Enabled Evaluation
A key benefit of Galleri is its ability to predict where in the body the cancer is coming from. The PATHFINDER 2 study demonstrated that the test correctly identified the Cancer Signal Origin (CSO) 92% of the time, leading to efficient diagnostic workups.
Diagnostic resolution took a median of 46 days, and only 0.6% of all participants had an invasive procedure (159/25,114). Invasive procedures were two times more common in participants with cancer than in those without.
MCED test safety was evaluated in an analyzable cohort of 25,114 participants. No serious, study-related adverse events were reported during the diagnostic workup.
Data from this study will be submitted to the U.S. Food and Drug Administration (FDA) as part of the Galleri premarket approval (PMA) application, along with data from the prevalent screening round of the NHS-Galleri trial.
In addition, GRAIL will submit to the FDA a bridging analysis to compare performance of the version of Galleri used in the PATHFINDER 2 study and the NHS-Galleri trial to the updated version that GRAIL plans to submit to the FDA for premarket approval.
GRAIL expects to complete the PMA modular submission for Galleri, which is under a Breakthrough Device Designation, in the first half of 2026.
In the meantime, this technology needs to become affordable for all ages including people under 50 years old. The need for more research into how to treat early stage cancer is crucial because the weight of research to date has focused on late stage cancer. The broader the better for this amazing technology.
