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