BRAF V600-mutant metastatic melanoma are commonly treated using a combination of anti-BRAF and anti-MEK tyrosine kinase inhibitors (TKIs). The OPTIMEL trial aims to study the interest of therapeutic drug monitoring (TDM) of TKIs and circulating tumor DNA (ctDNA) detected in plasma of patients with metastatic melanoma for disease monitoring. 35 patients with metastatic melanoma and treated with dabrafenib and trametinib will be enrolled in this trial. Blood samples will be collected for the determination of TKIs concentration and ctDNA detection.

Inclusion Criteria:

• Men and women 18 years of age and older
• Histologic proven advanced skin melanoma (Stage IV or stage IIIc inoperable) with BRAF V600 mutation
• Patient who will treated with combined kinase inhibitors (dabrafenib + trametinib).
• Patient able to stand a blood collection of 20 mL
• Ability to provide an informed written consent form
• Patient must be affiliated to a social security system
• Patient's legal capacity to consent to study participation and to understand and comply with the requirements of the study.

Exclusion Criteria:

• Patient with mucosal melanoma
• Patient with non-metastatic skin melanoma (All stages except stage IV and stage III C inoperable)
• Patient with another synchronous cancer, or within 3 years
• Patient with a contraindication to blood collection of 20 mL
• Patient deprived of liberty or under supervision
• Patient unable to receive kinase inhibitor therapy
• Patient treated with another combined kinase inhibitors than dabrafenib and trametinib
• Pregnant or breastfeeding women
• Patient (man or woman) of childbearing age who does not agree to use of contraceptive methods validated during the study