Nima Nabavizadeh MD; ESMO Berlin: Multi-Cancer Early Detection Test: PATHFINDER II study Finds Early Promise

An interview with Nima Nabavizadeh MD, Associate Professor of Radiation Medicine, Oregon Health & Science University (OHSU), Portland, USA, Chief Medical Officer, Cancer Early Detection Research Center, Portland, Oregon.https://www.audiomedica.com/wp-content/2025/11/251107-Nima-Nabavizadeh-MD-ESMO-2024-PRODUCTION-MASTER.mp3

BERLIN, Germany—A pan-cancer early detection test, that identifies “methylation fingerprints” for a wide range of cancers, has been shown to find more cancers sooner than conventional screening according to research reported to the European Society for Medical Oncology (ESMO) 2025 Annual Congress.

Nima Nabavizadeh MD, Associate Professor of Radiation Medicine at the Oregon Health & Science University (OHSU) in Portland, USA, who is also Chief Medical Officer of the Cancer Early Detection Research Center in Portland, Oregon gave a report on the safety and performance of the test at the ESMO congress. Afterwards he spoke with our reporter, Peter Goodwin:

Audio Journal of Oncology: Nima Nabavizadeh MD

IN: “[GOODWIN]I am at the ESMO meeting …. OUT: ……of oncology. I’m Peter Goodwin” 9:55sec

ESMO ABSTRACT LBA64:

Safety and performance of a multi-cancer early detection (MCED) test in an intended-use population: Initial results from the registrational PATHFINDER II study

https://assets.grail.com/wp-content/uploads/2025/10/ESMO-2025_PF2-Initial-Results_Presentation_FINAL-CLEAN-10.16.2025.pdf

Speaker:

Nima Nabavizadeh (Portland, United States of America)

Authors:

Nima Nabavizadeh (Portland, United States of America) Charles McDonnell III (Sacramento, United States of America) Dax Kurbegov (Nashville, United States of America) Marc Matrana (New Orleans, United States of America) Shirish Gadgeel (Detroit, United States of America) Raymond H. Kim (Toronto, Canada) Gretchen Stipec (Fountain Valley, United States of America) Kevin Oeffinger (Durham, United States of America) Michael J. Demeure (Newport Beach, United States of America) Roland Matthews (Atlanta, United States of America) Rebecca Kaltman (Fairfax, United States of America) Tamar Toronjadze (Flushing, United States of America) Cora N. Sternberg (New York, United States of America) Jennifer Tran (Washington, United States of America) Natalia Colocci (Mountain View, United States of America) Leonardo Forero (Amarillo, United States of America) Margarita Lopatin (Menlo Park, United States of America) Margaret McCusker (Menlo Park, United States of America) Karthik Giridhar (Rochester, United States of America)

Background

The MCED test (Galleri®) detects cancer signals from cell-free DNA in blood and predicts cancer signal origin (CSO) to guide diagnostic (dx) evaluation. PATHFINDER 2 (PF2; NCT05155605) assesses its safety and performance in a large, diverse intended-use population.

Methods

PF2 is a prospective, multicenter, interventional study that enrolled participants (ppts) aged ≥50y with no clinical suspicion of cancer and no cancer diagnosis/treatment in the past 3y. Primary objectives were safety and performance of the MCED test. Ppts with an MCED cancer signal detected (positive) result underwent dx evaluation based on predicted CSO(s). This prespecified initial analysis included ppts with 12m follow-up (fu) as of Dec 31, 2024. A 3y fu is planned.

Results

35,878 ppts were enrolled. Of 23,161 performance analyzable ppts with 12m fu, 216 (0.93%) had a positive MCED test. Specificity was 99.6% (95% CI 99.5-99.7%); positive predictive value (PPV) was 61.6% (54.9-67.8%). First CSO prediction accuracy was 91.7% (85.8-95.3%). Episode sensitivity during 12m fu was 73.7% (65.6-80.4%) in a prespecified subgroup of 12 cancers responsible for ⅔ of US cancer deaths and 40.4% (35.3-45.8%) in all cancers. Of 329 ppts with cancer, 200 had screen-detected cancers: 133 by MCED testing (114 new primaries; 19 recurrent), 20 by USPSTF A/B and 47 by USPSTF C recommended screening tests. Of 133 MCED-detected cancers (MCED cancer detection rate: 0.57%), 75.2% do not have common screening options. Of 114 MCED-detected new primaries, 53.5% were stage I-II; 69.3% were stage I-III. Median time to dx resolution was 46d (IQR 42-59). Of 25,114 safety analyzable ppts, 159 (0.6%) had a protocol-directed invasive procedure. Invasive procedures were ∼2x more common for ppts dx with cancer vs not dx after a positive MCED test.

Conclusions

MCED testing increased the number of screen-detected cancers nearly 7-fold when added to USPSTF A/B recommended screening (3-fold when added to USPSTF A/B/C). Most MCED-detected new primaries were early stage. With PPV exceeding that of standard of care screening tests and a favorable safety profile, these initial PF2 results support the MCED test’s use for population-scale screening.

Clinical trial identification

NCT05155605.

Editorial acknowledgement

Medical writing support for the development of this abstract, under the direction of the authors, was provided by Jennifer Hepker, PhD, and Alexandra L. Thomas, PhD, of Citrus Health Group (Chicago, IL, USA), and was funded by GRAIL, Inc.