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