Tinostamustine and Nivolumab in Advanced Melanoma

• Status: Recruiting
• Trial end date: 2024-03-15
• Target enrollment: 0
• Participant gender: All

Summary

This trial is a first-in-human drug combination with the first-in-class alkylating histone deacetylase inhibition (HDACi) fusion molecule Tinostamustine (EDO-S101) and the anti-PD-1 monoclonal antibody Nivolumab in patients with refractory, locally advanced or metastatic melanoma.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Markus Joerger
• Treatments: Nivolumab

Criteria

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