PATHFINDER 2: A Multi-Cancer Early Detection Study

Study Overview
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Brief Summary
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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.

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

Conditions
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Early Detection of Cancer, Cancer

Intervention / Treatment
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* Device: Multi-Cancer Early Detection Test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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. 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)

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants 50 years of age or older<br>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<br>* Blood collection and multi-cancer early detection testing with return of results.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multi-cancer early detection, cancer screening, circulating cell-free tumor DNA, MCED