Inclusion Criteria:

          -  Age > 18 years

          -  Stage IV or un-resectable stage III melanoma

          -  Presence of BRAF V600E/K mutation and CDNKN2A loss and expression of Rb using
             immunohistochemistry in a recent metastatic sample (< 6 months)

          -  A previous exposure to BRAF inhibitor or combination of BRAF and MEK inhibitors
             therapy is allowed unless it has been stopped more than 3 months before study
             enrolment(This will defined the two strata of the trial)

          -  No previous therapy by MEK inhibitor unless associated with BRAF inhibitors

          -  No previous therapy with the AKT/PI3K pathway inhibitor

          -  Patients should have a tumour available for repeated biopsies for pharmacodynamics
             evaluation

          -  Life expectancy of > 3 months

          -  ECOG performance status <2

          -  Signed informed consent

          -  Patient with health insurance coverage

          -  No patient under guardianship or curators

        Exclusion Criteria:

          -  Inadequate hepatic function defined as serum bilirubin>25 μmol/l, transaminases > 3.0
             times the upper limit of normal (ULN) or 5ULN in cases of liver metastases;

          -  Inadequate bone marrow function defined as absolute neutrophil count<1500/mcl,
             platelets<150000/mcl and haemoglobin<8g/dL

          -  Inadequate renal function with serum creatinine>2.0mg/dl) and /or creatinine
             clearance< 60 ml/min

          -  Untreated brain metastases : Patients with brain metastases will be eligible if they
             have completed treatment 1 months prior to the start of study medication, have
             discontinued corticosteroid treatment for these metastases for at least 5 days, and
             are neurologically asymptomatic

          -  Myocardial infarct or unstable angina within the past 6 months

          -  Concomitant take of drugs known to be strong inhibitor or inducers of CYP314

          -  HIV positive.

          -  Chemotherapy, immunotherapy within 4 weeks

          -  Drugs interfering with PD-0332991 and vemurafenib metabolism

          -  Malabsorption syndrome or other condition that would interfere with enteral absorption

          -  Congenital long QT syndrome or screening QTc > 470 msec

          -  Need for chronic corticosteroid therapy of ≥10 mg of prednisone per day