A Prospective Study of Plasma Genotyping as a Noninvasive Biomarker for Genotype-directed Cancer Care

Inclusion Criteria

To participate in this study a participant must meet the eligibility of one of the
following cohorts:

Cohort 1: Cancers beginning initial treatment

- One of the following diagnoses:

- Cohort 1A (CLOSED):

---Advanced non-squamous NSCLC (including adenosquamous)

- Cohort 1B:

- Stage II-III non-squamous NSCLC (including adenosquamous)

- Stage IIIB-IV melanoma

- Patient must be planned to begin initial therapy, or completely resected before or
after receiving adjuvant therapy

- For patients with NSCLC, EGFR and KRAS genotype may be known or unknown

- For patients with melanoma, BRAF and NRAS genotype may be known or unknown

- For patients without tumor genotyping, there must be a plan for genotyping including
either:

- Archived tumor tissue available and planned for genotyping

- A biopsy at some future time is anticipated and will be available for genotyping

Cohort 2: Cancers with acquired resistance to targeted therapy

- One of the following diagnoses:

- Cohort 2A (CLOSED):

---Advanced NSCLC harboring a known EGFR mutation

- Cohort 2B:

- Advanced NSCLC harboring a targetable genotype other than EGFR

- Advanced melanoma harboring a known tumor genotype

- Clinical determination of progression targeted therapy, as evidence by plans to start
a new systemic treatment regimen, or obtain a biopsy to plan a new treatment regimen

- New systemic treatment regimen planned OR

- Re-biopsy for resistance genotyping planned

- Note, date of targeted therapy start and clinical progression must be provided

Cohort 3: Cancers with a known genotype starting palliative systemic therapy

Cohort 3A (CLOSED):

- Advanced NSCLC harboring one of the following mutations:

- EGFR exon 19 deletion

- EGFR L858R

- EGFR T790M

- KRAS G12X

- BRAF V600E

- Patients must be initiating palliative systemic therapy, either on or off a clinical
trial

Cohort 4: Paired plasma NGS and ddPCR

- Cohort 4A (CLOSED):

- Advanced NSCLC, newly diagnosed or with progression following treatment.

- Biopsy tissue must be available or a biopsy planned and one of the following:

- Genotyping must have been performed previously

- Genotyping must be in progress

- A plan must exist to order genotyping on existing tissue or a planned
re-biopsy

- Patient must not be eligible to enroll in cohort 1A or 2A due to:

- Not eligible for cohort 1A or 2A

- Eligible for cohort 1A or 2A but cohort has closed

- Cohort 4B: Undergenotyped NSCLC

- Advanced NSCLC, newly diagnosed or with progression following treatment.

- No known targetable genotype on prior tumor genotyping

- Biopsy planned for tumor genotyping

- Cohort 4C: EGFR-mutant NSCLC with acquired resistance

- Advanced EGFR-mutant NSCLC with progression on EGFR TKI

- Biopsy planned for resistance genotyping (e.g. T790M, etc)

Exclusion Criteria

- Participants who are unable to provide informed consent

- Participants who are 18 years of age or younger

- Participants who are unable to comply with the study procedures