Evaluation of Multi-Cancer Early Detection Testing in a High-Risk Population: The INFORM Study.

The purpose of this research study is to evaluate the possible benefits and harms of
screening with an investigational blood test designed to detect many types of cancer
early.

The name of the screening blood test being studied is:

-GRAIL Galleri test

Inclusion Criteria Group 1- Cancer Predisposition Syndrome:

- Age ≥ 22 for patients with TP53 germline pathogenic variants, age ≥ 35 for all other
variants in cancer predisposing genes

- Germline genetic testing revealed pathogenic germline variants in cancer
predisposing genes (list of genes typically tested listed in pre-screening document)

- Individuals with a clinically based diagnosis of a Cancer Predisposition Syndrome
(examples, neurofibromatosis, Fanconi Anemia, Ataxia-Telangiectasia)

Inclusion Criteria Group 2 - Familial Risk:

- Age ≥ 45

- Adults with family history suggestive of elevated cancer risk as defined by any the
criteria below, who do not fall into Group 1:

- ≥ 1 first or second degree relative on same side of the family with:

- Breast, colon, gastric, endometrial, kidney cancer at or before age 50

- Triple negative breast cancer (any age)

- Male breast cancer (any age)

- Ovarian, pancreatic, sarcoma cancer (any age)

- Neuroendocrine cancer or tumors (any age)

- Metastatic prostate cancer (any age)

- Multiple primary cancers (example bilateral breast cancer)

- ≥ 2 first or second degree relative on same side of the family (any combination
is acceptable) with breast or prostate cancer at any age

Exclusion Criteria:

- Individuals diagnosed with invasive malignancy within 3 years of enrollment

- Have had a blood-based multi-cancer screening test within last year

- Individuals with evidence of symptomatic or active cancer requiring active
therapeutic intervention at the time of participation (hormone therapy for
breast/prostate cancer is considered acceptable and will not preclude participation)

- Individuals in Group 2 whose family history of cancer was the result of a germline
mutation in a cancer predisposing gene and who have tested negative for that same
familial germline mutation

- Individuals in process of being evaluated for clinical suspicion of cancer

- Individuals who have undergone a cancer risk-reducing surgery for hereditary cancer
risk (e.g., mastectomy)

- Individuals with known hematologic precursor disease (e.g. CHIP, MGUS, etc.)

- Individuals without English-language proficiency