Unverblindete, nicht randomisierte Phase IB-Studie zur Bestimmung der Sicherheit, Verträglichkeit und empfohlenen Dosis von TINOSTAMUSTINE in Kombination mit Nivolumab bei Patienten mit fortgeschrittenem Melanom

Drug: Tinostamustine

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