PATHFINDER 2 Study Shows Improved Performance of Galleri Multicancer Detection Test

The Galleri multi-cancer early detection (MCED) test demonstrated substantially higher positive predictive value (PPV) in the PATHFINDER 2 registrational study compared to the previously published PATHFINDER study, according to top-line results announced June 18 by GRAIL, Inc.

The top-line results on Galleri performance and safety from the pre-specified analysis included the first 25,578 participants from the ongoing study of 35,878 adults over 50 years of age with no clinical suspicion of cancer and who qualify for for guideline-recommended cancer screening in the United States.

©GRAIL, Inc.

GRAIL initiated PATHFINDER 2 in 2021 to evaluate the safety and performance of adding the Galleri test to standard of care single cancer screening. The study builds on results from the original PATHFINDER study, which showed that adding Galleri to standard of care cancer screening more than doubled the overall number of cancers detected by screening.

Data from evaluable PATHFINDER 2 participants with 12 months of follow-up showed substantially higher PPV than that observed in the PATHFINDER study, though specific numerical values were not disclosed in the announcement. The original PATHFINDER study demonstrated a PPV of 43%, specificity of 99.5%, and 88% cancer signal origin (CSO) accuracy. PATHFINDER 2 maintained CSO accuracy and specificity consistent with the original study results. Grail reported no serious safety concerns in PATHFINDER 2.

"We are delighted to see very encouraging performance of the Galleri MCED test as a cancer screening tool in broad intended use populations of asymptomatic adults over 50 years of age in both the PATHFINDER 2 study and the NHS-Galleri trial's prevalent screening round," Josh Ofman, MD, MSHS, GRAIL president, said in the announcement.

The study's primary objectives evaluate the safety and effectiveness of the Galleri MCED test based on the number and type of diagnostic evaluations performed in participants who receive a "cancer signal detected" test result, and assess test performance across various measures, including PPV, negative predictive value (NPV), sensitivity, specificity, and CSO prediction accuracy. Participants who receive a cancer signal detected result undergo additional diagnostic testing based on the predicted CSO to determine cancer presence.

GRAIL plans to submit PATHFINDER 2 study results to the FDA as part of the Galleri premarket approval application (PMA), along with data from the prevalent screening round of the NHS-Galleri trial. The company will also submit bridging analyses comparing the performance of the Galleri version used in PATHFINDER 2 and NHS-Galleri to the updated version planned for FDA submission. The PMA proceeds through a modular submission under FDA Breakthrough Device Designation, with GRAIL expecting to complete the submission in the first half of 2026.

The company plans to submit detailed PATHFINDER 2 results for presentation at a leading international oncology meeting before year-end. The study includes secondary objectives examining utilization of guideline-recommended cancer screening procedures after MCED test use and participant reported outcomes over multiple time points, including assessments of participant anxiety and satisfaction with the test.

"We would like to extend our sincere gratitude to all of the participants and investigators in both of these pivotal studies, who are collectively helping to realize the potential of this groundbreaking technology for population-scale multi-cancer early detection and move the field forward. We look forward to sharing the detailed PATHFINDER 2 data at a medical congress later this year," Ofman concluded.

GRAIL announces positive topline results from the Galleri PATHFINDER 2 registrational study. News release. Grail, Inc. June 18, 2025. Accessed June 19, 2025. https://grail.com/press-releases/grail-announces-positive-top-line-results-from-the-galleri%e2%93%a1-pathfinder-2-registrational-study/