Tinostamustine and Nivolumab in Advanced Melanoma

Inclusion Criteria: * Written informed consent * Patients with either histologically or cytologically confirmed inoperable stage III or metastatic stage IV melanoma * Indication for the regular systemic treatment with the anti-PD-1 monoclonal antibody Nivolumab monotherapy * Patient received a maximum of 1 prior systemic palliative line of treatment * ECOG ≤2 * Patients with brain metastases must have undergone definitive treatment (surgery or radiotherapy) at least 2 weeks prior to starting study drug and be documented as having stable disease by imaging * Adequate bone marrow, renal and hepatic function * Adequate contraception Exclusion Criteria: * Prior treatment with a PD-(L)1 targeted monoclonal antibody * Patients who have received systemic treatments or radiotherapy within 2 weeks prior to starting study drug * Concomittant treatment with systemic steroids at a daily dose equivalent to ≥10mg of prednisone, or concomittant treatment with immunosuppressive drugs such as methotrexate * Patients with a prior malignancy are excluded (except non-melanoma skin cancers, and in situ cancers such as the following: bladder, colon,cervical/dysplasia, melanoma, or breast). Patients with other second malignancies diagnosed more than 2 years ago who have received therapy with curative intent with no evidence of disease during the interval who are considered by the Investigator to present a low risk for recurrence will be eligible. * NYHA stage III/IV congestive heart failure and/or arrhythmia not adequately controlled * QTc interval (Fridericia's formula) \> 450msec * Patients who are on treatment with drugs known to prolong the QT/QTc interval (Credible Meds list: Known risk of TdP. https://www.crediblemeds.org). * Pregnant and breast feeding patients