PATHFINDER 2: A Multi-Cancer Early Detection Study

The PATHFINDER 2 Study: Evaluating the Safety and Performance of the GRAIL Multi-Cancer Early Detection Test in an Eligible Screening Population

This is a prospective, multi-center interventional study of the GRAIL multi-cancer early detection (MCED) test with return of test results for participants enrolled through healthcare systems in North America. The purpose of this study is to evaluate the safety and performance of the GRAIL MCED test in a population of individuals who are eligible for guideline-recommended cancer screening. In cases with a "cancer signal detected" test result, participants will undergo diagnostic procedures based on the test returned cancer signal origin(s) to determine if they have cancer. The number and types of diagnostic procedures required to achieve diagnostic resolution will be assessed. Participant-reported outcomes will be collected at several time points to assess participants' perceptions about the multi-cancer early detection test.

The study will enroll approximately 35,000 and no more than 38,500 participants as defined by eligibility criteria over an anticipated enrollment period of approximately 36 months at up to 40 clinical institutions within North America. Participants will be actively followed for approximately 3 years from the date of their enrollment.

Study Overview

• Status: Active, not recruiting
• Conditions: Cancer; Early Detection of Cancer
• Intervention / Treatment: Device: Multi-Cancer Early Detection Test

• Study Type: Interventional
• Enrollment (Actual): 35883
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C1
      • University Health Network
• United States
  • California
    • Auburn, California, United States, 95602
      • Sutter Health
    • Davis, California, United States, 95616
      • Sutter Health
    • Elk Grove, California, United States, 95758
      • Sutter Health
    • Fairfield, California, United States, 94534
      • Sutter Health
    • Irvine, California, United States, 92663
      • HOAG Irvine
    • Irvine, California, United States, 92663
      • HOAG Vivante Newport Mesa
    • Long Beach, California, United States, 90806
      • Long Beach Memorial Medical Center
    • Modesto, California, United States, 95355
      • Sutter Health
    • Newport Beach, California, United States, 92663
      • HOAG Newport Beach
    • Palo Alto, California, United States, 94301
      • Palo Alto Medical Foundation
    • Sacramento, California, United States, 95816
      • Sutter Health
    • Santa Cruz, California, United States, 95062
      • PAMF - Santa Cruz
    • Sunnyvale, California, United States, 94086
      • PAMF - Sunnyvale
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Sarah Cannon Research Institute - Englewood Primary Care
  • District of Columbia
    • Northwest, District of Columbia, United States, 20010
      • Medstar Washington Hospital Center
  • Florida
    • Pensacola, Florida, United States, 32503
      • Woodlands Medical Specialists
  • Georgia
    • Atlanta, Georgia, United States, 30310
      • Morehouse School of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60608
      • University of Illinois at Chicago
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70836
      • Ochsner Grove
    • Lafayette, Louisiana, United States, 70503
      • Ochsner Lafayette General
    • New Orleans, Louisiana, United States, 70127
      • Ochsner Health
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Maryland Oncology Hematology
  • Michigan
    • Clinton, Michigan, United States, 48038
      • Henry Ford Macomb
    • Dearborn, Michigan, United States, 48126
      • Henry Ford Medical Center Ford Road
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Detroit, Michigan, United States, 48207
      • Henry Ford Medical Center Harbortown
    • Detroit, Michigan, United States, 48235
      • Henry Ford Medical Center Detroit North West
    • Sterling Heights, Michigan, United States, 48310
      • Henry Ford Medical Center Sterling Heights
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Cancer Center
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medicine
    • Queens, New York, United States, 11355
      • Flushing Hospital Medical Center
    • Queens, New York, United States, 11418
      • Jamaica Hospital Medical Center
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Sarah Cannon Asheville Family Medicine
    • Durham, North Carolina, United States, 27705
      • Duke University Health System
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma
  • Oregon
    • Bend, Oregon, United States, 97701
      • St. Charles Health System
    • Coos Bay, Oregon, United States, 97420
      • Oregon Health & Science University Bay Area Hospital
    • Portland, Oregon, United States, 97201
      • Oregon Health & Science University Knight Cancer Institute
    • Salem, Oregon, United States, 97301
      • SALEM Health
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute - The Frist Clinic
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon, Centennial Internal Medicine Continuity Clinic
  • Texas
    • Amarillo, Texas, United States, 79106
      • Texas Oncology - West Texas
    • Austin, Texas, United States, 78758
      • Sarah Cannon, Austin Diagnostic Clinic
    • Houston, Texas, United States, 77014
      • Kelsey-Seybold Clinic Cypress Woods
    • Houston, Texas, United States, 77025
      • Kelsey-Seybold Clinic Holcombe
    • Plano, Texas, United States, 75093
      • Texas Oncology - Plano West
    • Plano, Texas, United States, 75075
      • Texas Oncology - Plano East
    • San Antonio, Texas, United States, 78229
      • University Texas Health San Antonio - Mays Cancer Center
    • Tyler, Texas, United States, 75702
      • Texas Oncology - Tyler
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova
    • Norfolk, Virginia, United States, 23510
      • Eastern Virginia Medical School
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University
  • Washington
    • Vancouver, Washington, United States, 98684
      • Northwest Cancer Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Participants must be at least 50 years of age, inclusive, at the time of signing the Informed Consent Form (ICF).
2. Participants must be capable of giving signed and legally effective informed consent

Exclusion Criteria:

1. Undergoing or referred for diagnostic evaluation due to clinical suspicion for cancer (e.g., referred to a medical or surgical oncologist, or scheduled for biopsy on the basis of a suspicious imaging abnormality).

2. Personal history of invasive solid tumor or hematologic malignancy, diagnosed within the 3 years prior to expected enrollment date, or diagnosed greater than 3 years prior to expected enrollment date and never treated.

   • Individuals with a diagnosis of non-metastatic basal cell carcinoma and squamous cell carcinoma of the skin are not excluded.

3. Prior/Concurrent Concomitant Therapy (Medications/Treatments):

   • Definitive treatment for invasive solid tumor or hematologic malignancy within the 3 years prior to expected enrollment date. Adjuvant hormone therapy for cancer (e.g. for breast or prostate cancer) is not an exclusion criterion.
4. Individuals who will not be able to comply with the protocol procedures.
5. Individuals who are not currently registered patients at a participating center.
6. Previous or current participation in another GRAIL-sponsored study. "Participation" is defined as having signed consent and provided a blood sample.
7. Previous or current employees or contractors of GRAIL.
8. Current pregnancy (by self-report of pregnancy status)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants 50 years of age or older; The study will aim to enroll a diverse participant population generally representative of the US population with respect to race, ethnicity, and sex. The target age categories of 60-69 years and 70-79 years will be enriched to increase the number of cancer events that are observed during the study.	Device: Multi-Cancer Early Detection Test; Blood collection and multi-cancer early detection testing with return of results.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety: Number and type of invasive procedures performed in participants with a cancer signal detected by the multi-cancer early detection (MCED) test and no cancer diagnosis at the time of diagnostic resolution (i.e., false positive test result).	Up to 3 Years
Test performance: diagnosis of invasive cancer, assessed by positive predictive value (PPV).	Up to 3 Years
Test performance: diagnosis of invasive cancer, assessed by negative predictive value (NPV).	Up to 3 Years
Test performance: diagnosis of invasive cancer, assessed by sensitivity.	Up to 3 Years
Test performance: diagnosis of invasive cancer, assessed by specificity.	Up to 3 Years
Test performance: diagnosis of invasive cancer, assessed by cancer signal origin (CSO) accuracy.	Up to 3 Years
Test performance: diagnosis of invasive cancer, assessed by observed cancer detection rate (CDR).	Up to 3 Years
Test performance: diagnosis of invasive cancer, assessed by number needed to screen to detect an invasive cancer (NNS).	Up to 3 Years

Secondary Outcome Measures

Outcome Measure	Time Frame
Participant-reported anxiety resulting from use of the multi-cancer early detection (MCED) test assessed via questionnaire at various time points during the study.	Up to 3 Years
Participant-reported intention to follow and use guideline recommended cancer screening procedures after use of the multi-cancer early detection (MCED) test assessed via questionnaire at various time points during the study.	Up to 3 Years
Cancer detection rate of confirmatory PET-CT in participants for whom cancer signal origin directed workups do not result in diagnosis of cancer.	Up to 3 Years
Number and type of diagnostic evaluations (imaging procedures, invasive procedures, laboratory test) by predicted cancer signal origin and outcome of diagnostic resolution.	Up to 3 Years
Per-participant radiation exposure during diagnostic evaluation for test positive participants.	Up to 3 Years
Accuracy of initial multi-cancer early detection (MCED) test result and cancer signal origin prediction, among the subset of participants with a research blood draw.	Up to 3 Years
Participants-reported perceptions about the multi-cancer early detection (MCED) test including satisfaction with the MCED tests and attitudes towards subsequent MCED testing assessed via questionnaire at various time points during the study.	Up to 3 Years

Collaborators and Investigators

• Sponsor: GRAIL, Inc.
• Investigators: Study Director: Celine Marquez, MD, GRAIL, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2021
• Primary Completion (Actual): February 11, 2026
• Study Completion (Estimated): April 30, 2028

Study Registration Dates

• First Submitted: November 16, 2021
• First Submitted That Met QC Criteria: November 30, 2021
• First Posted (Actual): December 13, 2021

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: cancer screening; multi-cancer early detection; circulating cell-free tumor DNA; MCED
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: GRAIL-012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No