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)

Cohort 5: Genotyped KRAS patients starting palliative systemic therapy

Advanced NSCLC harboring a KRAS exon 2 mutation
Patients must be initiating new systemic therapy, either on or off a clinical trial

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