To Evaluate the Efficacy Beyond Progression of Vemurafenib+Cobimetinib Associated With Local Treatment Compared to Second-line Treatment in Patients With BRAFV600+ Metastatic Melanoma in Focal Progression With First-line+Vemurafenib+Cobimetinib.

Inclusion Criteria:

* Patients with histologically confirmed melanoma, either unresectable Stage IIIc or Stage IV metastatic melanoma, as defined by the American Joint Committee on Cancer 7th edition
* Patients previously untreated for metastatic melanoma
* Documentation of BRAFV600 mutation-positive status in melanoma tumor tissue (archival or newly obtained tumor samples) by a validated mutational test
* Adequate performance status to receive vemurafenib and cobimetinib therapy as determined by treating physician
* Male or female patient aged ≥18 years
* Able to participate and willing to give written informed consent prior to any treatment-related procedures and to comply with treatment guidance
* Adequate end-organ function, defined by the following laboratory results obtained within 14 days prior to the first dose of program drug treatment:

  1. Bilirubin ≤ 1.5 x the upper limit of normal (ULN).
  2. AST, ALT, and alkaline phosphatase ≤ 3 x ULN, with the following exceptions:

     * Patients with documented liver metastases: AST and/or ALT ≤ 5 x ULN.
     * Patients with documented liver or bone metastases: alkaline phosphatase ≤ 5 x ULN.
  3. Serum creatinine ≤1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min based on measured CrCl from a 24-hour urine collection or Cockroft-Gault glomerular filtration rate estimation.
* Female patients of childbearing potential and male patients with partners of childbearing potential must agree to always use two effective forms of contraception during program therapy and for at least 6 months after completion of program therapy
* Negative serum pregnancy test prior to commencement of dosing in women of childbearing potential
* Patient should be able to swallow tablets
* Absence of any psychological, familial, sociological, or geographical condition that potentially hampers compliance with the treatment regimen
* Patient does not currently participate in other clinical trials

Exclusion Criteria:

* Palliative radiotherapy within 7 days prior to the first dose of program treatment
* Patients with active malignancy (other than BRAF-mutated melanoma) or a previous malignancy within the past 3 years except for patients with resected melanoma, resected BCC, resected cutaneous SCC, resected melanoma in situ, resected carcinoma in situ of the cervix, and resected carcinoma in situ of the breast
* Evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment / central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
* Systemic risk factor for RVO including uncontrolled glaucoma, uncontrolled hypercholesterolemia, hypertriglyceridemia or hyperglycemia
* History of clinically significant cardiac dysfunction, including the following:

  1. Current unstable angina.
  2. Symptomatic congestive heart failure of New York Heart Association class 2 or higher.
  3. History of congenital long QT syndrome or mean (average of triplicate measurements) QTcF ≥ 450 msec at baseline; presence of clinically significant ventricular or atrial dysrhythmias ≥ Grade 2.
  4. Uncontrolled hypertension ≥ Grade 2 (patients with a history hypertension controlled with anti-hypertensives to ≤ Grade 1 are eligible).
  5. Left ventricular ejection fraction (LVEF) below institutional lower limit of normal (LLN) or below 50%, whichever is lower
* Current severe, uncontrolled systemic disease
* Major surgery or traumatic injury within 14 days prior to first dose of program treatment
* History of malabsorption or other condition that would interfere with absorption of program drugs
* Hypersensitivity to the active substance or to any of the excipients
* Pregnant or breastfeeding women