1. Safety and dose-limiting toxicity (Time Frame - at 6 weeks): Dose limiting toxicity defined as any of the following AEs (according to CTCAE v 4.03) occurring during the first 42 days of study treatment for each study patient of the safety part of the trial, and regarded to be related (possibly, probably or definitely) to Tinostamustine:
CTC °4 neutropenia during ≥ 5 days
Febrile neutropenia
CTC °4 thrombocytopenia or CTC° 3 thrombocytopenia with bleeding
Any other ≥ CTC °4 hematological AE
≥ CTC °3 AST or ALT elevations for >7 days, or CTC °4 AST/ALT elevations for any duration
≥ CTC °3 nausea, vomiting or diarrhea despite appropriate pre-medication
Any other ≥ CTC °3 non-hematological study-treatment-related AE, excluding alopecia
≥ CTC °3 uveitis, pneumonitis, bronchospasm, neurological toxicity, hypersensi-tivity reactions or infusion reactions that result in discontinuation of study treat-ment
Any study treatment-related AE that results in a delay of the administration of Tinostamustine of at least 4 weeks
Secondary outcome:
1. Overall safety profile of the tinostamustine/nivolumab drug combination (Time Frame - during a maximum 2 years of study treatment plus 100 days thereafter (3 years)): All adverse events (AE) including laboratory safety parameters according to CTCAE v.4.03
2. Radiological response (Time Frame - every 8 weeks until progressive disease or end of study (5 years)): Objective tumor response according to RECIST 1.1 and iRECIST
3. Progression-free survival (Time Frame - through study completion (5 years)): Progression-free survival (PFS, iPFS), defined as the time between registration to the study and the time of disease progression according to RECIST v.1.1 and iRECIST or death of the patient, whatever occurs first
4. Overall survival (Time Frame - through study completion (5 years)): Overall survival (OS) from registration of study participation
