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