903O - A prospective study of a multi-cancer early detection blood test

Background

A validated blood-based multi-cancer early detection (MCED) test uses cfDNA and machine learning to detect a common cancer signal across >50 cancer types and predict cancer signal origin (CSO). PATHFINDER is a prospective study in a screening population that evaluated the clinical feasibility of MCED testing.

Methods

Participants were aged ≥50 y with or without additional cancer risk factors. Blood samples were collected, cfDNA analyzed, and MCED test results returned (MCED-E, early version). Cancer status was confirmed at 1 year for all participants. The primary outcome was the extent of diagnostic testing required for resolution after cancer signal detected by MCED-E. Those with cancer signal and confirmed cancer are true positive (TP), without confirmed cancer are false positive (FP). Diagnostic evaluation was at the discretion of the treating physician. Key secondary outcomes included test performance and safety. A pre-specified analysis evaluated a refined test version (MCED-Scr) using the participants’ banked specimens without return of results.

Results

The MCED-E test detected cancer signal in 1.4% (92/6621) of participants with analyzable samples. Cancer was confirmed in 38% (35/92). Specificity was 99.1% (6235/6290). See table for primary and secondary outcomes. A total of 73% (24/33) of TPs had diagnostic resolution in <3 months. MCED-Scr performance was similar with MCED-E (Table). Four AEs were reported (0.06%); none were due to confirmatory diagnostic procedures. Table: 903O

Conclusions

MCED testing was feasible in outpatient practice without significant AEs and with a PPV of approximately 40%. Studies to refine multi-cancer screening techniques are ongoing.

Clinical trial identification

NCT04241796.

Editorial acknowledgement

We acknowledge Jennifer Hepker, PhD and Merrilee Johnstone, PhD (Prescott Medical Communications Group, Chicago, IL) and Neva West, PhD (NeuroWest Solutions, Seattle, WA) for medical writing, editorial, and administrative support that was funded by GRAIL LLC a subsidiary of Illumina Inc. currently held separate from Illumina Inc. under the terms of the Interim Measures Order of the European Commission dated 29 October 2021.

Legal entity responsible for the study

GRAIL LLC a subsidiary of Illumina Inc. currently held separate from Illumina Inc. under the terms of the Interim Measures Order of the European Commission dated 29 October 2021.

Funding

GRAIL LLC a subsidiary of Illumina Inc. currently held separate from Illumina Inc. under the terms of the Interim Measures Order of the European Commission dated 29 October 2021.

Disclosure

D. Schrag: Non-Financial Interests, Institutional, Advisory Role: GRAIL, LLC, a subsidiary of Illumina, Inc., Journal of the American Medical Association; Financial Interests, Institutional, Research Grant: GRAIL, LLC, a subsidiary of Illumina, Inc., Dana-Farber Cancer Institute; Financial Interests, Institutional, Speaker's Bureau: Pfizer. C.H. McDonnell III: Financial Interests, Institutional, Stocks/Shares: Sutter Medical Group. L. Nadauld: Financial Interests, Personal, Stocks/Shares: CitizenCorporation, Clarifi, Guidance Genomics. E.A. Klein: Non-Financial Interests, Institutional, Advisory Role: GRAIL, LLC, a subsidiary of Illumina, Inc., Genome Health; Financial Interests, Institutional, Research Grant: GenomeDx Biosciences. K.C. Chung: Financial Interests, Institutional, Full or part-time Employment: GRAIL, LLC, a subsidiary of Illumina, Inc. M. Lopatin: Financial Interests, Institutional, Full or part-time Employment: GRAIL, LLC, a subsidiary of Illumina, Inc. E.T. Fung: Financial Interests, Institutional, Full or part-time Employment: GRAIL, LLC, a subsidiary of Illumina, Inc. T.M. Beer: Financial Interests, Institutional, Advisory Role: GRAIL, LLC, a subsidiary of Illumina, Inc., AbbVie, Amgen, Astellas Pharma, AstraZeneca, Bayer, Constellation, Janssen, Myovant Sciences, Pfizer, Sanofi, Sapience Therapeutics, Bristol Meyers Squib, Clovis Oncology, Dantari Pharmaceuticals, GlaxoSmithKline, Novartis, Tolero; Financial Interests, Personal and Institutional, Stocks/Shares: Arvinas, Inc.; Financial Interests, Personal, Stocks/Shares: Salarius Pharmaceuticals, LLC; Other, Institutional, Research Grant, Grant paid to Institution: AllianceFoundation Trials, Astellas Pharma, Bayer, Boehringer Ingelheim, Corcept Therapeutics, Endocyte Inc., Exact Sciences Corp., Freenome, GRAIL, LLC, a subsidiary of Illumina, Inc., Harpoon Therapeutics, Janssen Research & Development, Medivation, Inc., Merck, Sotio, Theraclone Sciences/OncoResponse, Zenith Epigenetics. All other authors have declared no conflicts of interest.