Adaptive BRAF-MEK Inhibitor Therapy for Advanced BRAF Mutant Melanoma

Inclusion Criteria

• •Patients must be 18 years of age or above
• •Subjects must have cytologically or histologically-confirmed unresectable melanoma that harbors a BRAF V600E mutation determined by pyrosequencing assay or equivalent genotyping assay in a Clinical Laboratory Improvement Act (CLIA) certified laboratory, meeting one of the following American Joint Committee on Cancer (AJCC) (8th edition) staging criteria:
• •AJCC stage IV
• •AJCC stage IIIC or IIID with unresectable nodal/locoregional involvement
• •Subjects must have baseline plasma ctDNA \>= 0.5 copy/ul at time of study enrollment
• •Hemoglobin \>= 8.0 g/dL
• •Absolute neutrophil count \>= 1,500/mcL
• •Platelets \>= 75,000/mcL
• •Total bilirubin =\< 2 institutional upper limit of normal (ULN), unless suspected Gilbert's syndrome
• •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x institutional ULN (in participants with liver metastases =\< 5 x ULN)
• •Creatinine =\< 2.0 institutional ULN
• •Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
• •Negative serum pregnancy test within 7 days prior to commencement of dosing in premenopausal women. Women of non-childbearing potential may be included without serum pregnancy test if they are either surgically sterile or have been postmenopausal for \>= 1 year
• •Fertile men and women must use an effective method of contraception during treatment and for at least 6 months after completion of treatment as directed by their physician. (NOTE: Patients must agree to not use hormonal contraceptives, as encorafenib can result in decreased concentration and loss of efficacy.)
• •Patients on non-biologic disease modifying agents (e.g. methotrexate) or patients on corticosteroids =\< 10 mg prednisone daily or equivalent are permitted to enroll
• •Patients must not have had grade 3 or 4 immune-related adverse events on nivolumab that required more than 12 weeks of immune suppression with corticosteroids
• •No anti-PD-1/PD-L1 or BRAF/MEK inhibitor therapy in the metastatic setting is allowed; these treatments are allowed if given in neoaduvant or adjuvant setting \> 24 weeks ago. Prior radiation therapy is permitted. All adverse events associated with prior systemic therapy or radiation therapy must have resolved to =\< grade 1 prior to start of study
• •Subjects must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1