Early Detection of CancerNCT05155605
PATHFINDER 2: A Multi-Cancer Early Detection Study
A study testing Multi-Cancer Early Detection Test in people with Early Detection of Cancer and Cancer, run by GRAIL, Inc. at 56 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 50 years and olderHealthy volunteers can take part
- Conditions the study is for
- Early Detection of Cancer, Cancer
- What is being tested?
- Multi-Cancer Early Detection Test
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35,883 participants
- Where
- 56 sitesin 2 countries
- Study dates
- 8 Dec 2021to 30 Apr 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Participants must be at least 50 years of age, inclusive, at the time of signing the Informed Consent Form (ICF).
- Participants must be capable of giving signed and legally effective informed consent
Who cannot join
- 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).
- 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.
- 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.
- Individuals who will not be able to comply with the protocol procedures.
Show all 10Show fewer
- Individuals who are not currently registered patients at a participating center.
- Previous or current participation in another GRAIL-sponsored study. "Participation" is defined as having signed consent and provided a blood sample.
- Previous or current employees or contractors of GRAIL.
- Current pregnancy (by self-report of pregnancy status)
Trial locations and contacts
56 sites in 2 countries.
56 sites in 2 countries
United States55 sites
Texas Oncology - West Texas
Amarillo, Texas, 79106
Maryland Oncology Hematology
Annapolis, Maryland, 21401
Sarah Cannon Asheville Family Medicine
Asheville, North Carolina, 28801
Morehouse School of Medicine
Atlanta, Georgia, 30310
Sutter Health
Auburn, California, 95602
Sarah Cannon, Austin Diagnostic Clinic
Austin, Texas, 78758
Ochsner Grove
Baton Rouge, Louisiana, 70836
St. Charles Health System
Bend, Oregon, 97701
University of Illinois at Chicago
Chicago, Illinois, 60608
Cleveland Clinic
Cleveland, Ohio, 44195
Henry Ford Macomb
Clinton, Michigan, 48038
Oregon Health & Science University Bay Area Hospital
Coos Bay, Oregon, 97420
Sutter Health
Davis, California, 95616
Henry Ford Medical Center Ford Road
Dearborn, Michigan, 48126
Henry Ford Health System
Detroit, Michigan, 48202
Henry Ford Medical Center Harbortown
Detroit, Michigan, 48207
Henry Ford Medical Center Detroit North West
Detroit, Michigan, 48235
Duke University Health System
Durham, North Carolina, 27705
Sutter Health
Elk Grove, California, 95758
Sarah Cannon Research Institute - Englewood Primary Care
Englewood, Colorado, 80113
Inova
Fairfax, Virginia, 22031
Sutter Health
Fairfield, California, 94534
Kelsey-Seybold Clinic Cypress Woods
Houston, Texas, 77014
Kelsey-Seybold Clinic Holcombe
Houston, Texas, 77025
HOAG Irvine
Irvine, California, 92663
HOAG Vivante Newport Mesa
Irvine, California, 92663
Ochsner Lafayette General
Lafayette, Louisiana, 70503
Long Beach Memorial Medical Center
Long Beach, California, 90806
Sutter Health
Modesto, California, 95355
Sarah Cannon Research Institute - The Frist Clinic
Nashville, Tennessee, 37203
Sarah Cannon, Centennial Internal Medicine Continuity Clinic
Nashville, Tennessee, 37203
Ochsner Health
New Orleans, Louisiana, 70127
Weill Cornell Medicine
New York, New York, 10065
HOAG Newport Beach
Newport Beach, California, 92663
Eastern Virginia Medical School
Norfolk, Virginia, 23510
Medstar Washington Hospital Center
Northwest, District of Columbia, 20010
University of Oklahoma
Oklahoma City, Oklahoma, 73104
Palo Alto Medical Foundation
Palo Alto, California, 94301
Woodlands Medical Specialists
Pensacola, Florida, 32503
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
Texas Oncology - Plano East
Plano, Texas, 75075
Texas Oncology - Plano West
Plano, Texas, 75093
Oregon Health & Science University Knight Cancer Institute
Portland, Oregon, 97201
Flushing Hospital Medical Center
Queens, New York, 11355
Jamaica Hospital Medical Center
Queens, New York, 11418
Virginia Commonwealth University
Richmond, Virginia, 23219
Mayo Clinic - Cancer Center
Rochester, Minnesota, 55905
Sutter Health
Sacramento, California, 95816
SALEM Health
Salem, Oregon, 97301
University Texas Health San Antonio - Mays Cancer Center
San Antonio, Texas, 78229
PAMF - Santa Cruz
Santa Cruz, California, 95062
Henry Ford Medical Center Sterling Heights
Sterling Heights, Michigan, 48310
PAMF - Sunnyvale
Sunnyvale, California, 94086
Texas Oncology - Tyler
Tyler, Texas, 75702
Northwest Cancer Specialists
Vancouver, Washington, 98684
About this study
Official title: 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.
- Conditions
- Early Detection of Cancer, Cancer
- Being tested
- Multi-Cancer Early Detection Test
- Keywords
- multi-cancer early detection, cancer screening, circulating cell-free tumor DNA, MCED
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multi-Cancer Early Detection TestDevice
Blood collection and multi-cancer early detection testing with return of results.
| Study group | Role | What they receive |
|---|---|---|
| Participants 50 years of age or older | Experimental | 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. Receives: Device: Multi-Cancer Early Detection Test |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Up to 3 Years
Test performance: diagnosis of invasive cancer, assessed by positive predictive value (PPV).
Measured: Up to 3 Years
Test performance: diagnosis of invasive cancer, assessed by negative predictive value (NPV).
Measured: Up to 3 Years
Test performance: diagnosis of invasive cancer, assessed by sensitivity.
Measured: Up to 3 Years
Test performance: diagnosis of invasive cancer, assessed by specificity.
Measured: Up to 3 Years
Test performance: diagnosis of invasive cancer, assessed by cancer signal origin (CSO) accuracy.
Measured: Up to 3 Years
Test performance: diagnosis of invasive cancer, assessed by observed cancer detection rate (CDR).
Measured: Up to 3 Years
Test performance: diagnosis of invasive cancer, assessed by number needed to screen to detect an invasive cancer (NNS).
Measured: Up to 3 Years
Secondary outcomes (7)
Participant-reported anxiety resulting from use of the multi-cancer early detection (MCED) test assessed via questionnaire at various time points during the study.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 3 Years
Per-participant radiation exposure during diagnostic evaluation for test positive participants.
Measured: 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.
Measured: 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.
Measured: Up to 3 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2021
- Study start8 Dec 2021
- Primary completion11 Feb 2026
- Study completion30 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Early Detection of CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35,883 participants (actual)
Sponsor and investigators
- Lead sponsor
- GRAIL, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Celine Marquez, MD, Study director, GRAIL, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05155605
- Sponsor's protocol ID
- GRAIL-012
- Status last verified
- Apr 2026
- First submitted
- 16 Nov 2021
- Last updated
- 14 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Nabavizadeh N, McDonnell C, Kurbegov D, Matrana M, Gadgeel S, Kim RH, Stipec G, Oeffinger KC, Demeure MJ, Lillard JW Jr, Kaltman R, Tran J, Roth A, Tahhan S, Poklepovic A, Richards D, Lopatin M, Marquez C, McCusker M, Giridhar KV. Performance and safety of a multi-cancer early detection test: the PATHFINDER 2 study. Nat Med. 2026 Sep 22. doi: 10.1038/s41591-026-04618-w. Online ahead of print.
PubMed 42773207
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The PATHFINDER 2 Study: Evaluating the Safety and Performance of the GRAIL Multi-Cancer Early Detection Test in an Eligible Screening Population
- ClinicalTrials.gov ID
- NCT05155605
- Acronym / sponsor ID
- GRAIL-012
- Conditions
- Early Detection of Cancer, Cancer
- Keywords
- multi-cancer early detection, cancer screening, circulating cell-free tumor DNA, MCED
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 35,883 participants (actual)
- Lead sponsor
- GRAIL, Inc.Industry (pharma, biotech, devices)
- Study start
- 8 Dec 2021 (actual)
- Primary completion
- 11 Feb 2026 (actual)
- Study completion
- 30 Apr 2028 (estimated)
- First posted
- 13 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Participants 50 years of age or older | Experimental | Device: Multi-Cancer Early Detection TestThe 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. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Participants must be at least 50 years of age, inclusive, at the time of signing the Informed Consent Form (ICF).
- Participants must be capable of giving signed and legally effective informed consent
Key exclusion criteria (10 listed)
- 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).
- 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.
- Prior/Concurrent Concomitant Therapy (Medications/Treatments):
- Individuals who will not be able to comply with the protocol procedures.
- Individuals who are not currently registered patients at a participating center.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Multi-Cancer Early Detection TestBlood collection and multi-cancer early detection testing with return of results. | Device | Participants 50 years of age or older |
Primary outcome
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).
Time frame: Up to 3 Years
Test performance: diagnosis of invasive cancer, assessed by positive predictive value (PPV).
Time frame: Up to 3 Years
Test performance: diagnosis of invasive cancer, assessed by negative predictive value (NPV).
Time frame: Up to 3 Years
Test performance: diagnosis of invasive cancer, assessed by sensitivity.
Time frame: Up to 3 Years
Test performance: diagnosis of invasive cancer, assessed by specificity.
Time frame: Up to 3 Years
Test performance: diagnosis of invasive cancer, assessed by cancer signal origin (CSO) accuracy.
Time frame: Up to 3 Years
Test performance: diagnosis of invasive cancer, assessed by observed cancer detection rate (CDR).
Time frame: Up to 3 Years
Test performance: diagnosis of invasive cancer, assessed by number needed to screen to detect an invasive cancer (NNS).
Time frame: Up to 3 Years
7 secondary outcomes
Participant-reported anxiety resulting from use of the multi-cancer early detection (MCED) test assessed via questionnaire at various time points during the study.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 3 Years
Per-participant radiation exposure during diagnostic evaluation for test positive participants.
Time frame: 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.
Time frame: 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.
Time frame: Up to 3 Years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2026.
- Derived from this study: PubMed 42773207Nabavizadeh N, McDonnell C, Kurbegov D, Matrana M, Gadgeel S, Kim RH, Stipec G, Oeffinger KC, Demeure MJ, Lillard JW Jr, Kaltman R, Tran J, Roth A, Tahhan S, Poklepovic A, Richards D, Lopatin M, Marquez C, McCusker M, Giridhar KV. Performance and safety of a multi-cancer early detection test: the PATHFINDER 2 study. Nat Med. 2026 Sep 22. doi: 10.1038/s41591-026-04618-w. Online ahead of print.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Celine Marquez, MD study director
GRAIL, Inc.
56 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Multi-Cancer Early Detection Test in people with Early Detection of Cancer and Cancer, run by GRAIL, Inc. at 56 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 14 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 56 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). (time frame: Up to 3 Years). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05155605, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2026.