Tinostamustine and Nivolumab in Advanced Melanoma

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03903458
• Date of registration: 13/03/2019
• Prospective Registration: No
• Primary sponsor: Markus Joerger
• Public title: Tinostamustine and Nivolumab in Advanced Melanoma ENIgMA
• Scientific title: Open Label, Non-randomized, Phase IB Study to Characterize Safety, Tolerability and Recommended Dose of Tinostamustine and Nivolumab in Patients With Refractory, Locally Advanced or Metastatic MelAnoma
• Date of first enrolment: March 7, 2019
• Target sample size: 21
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT03903458
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Switzerland

Contacts

• Name: Elke Hiendlmeyer, Dr.

• Name: Markus Joerger, Prof.
• Affiliation: Cantonal Hospital St. Gallen, Switzerland

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Malignant Melanoma

Intervention(s)

Drug: Tinostamustine

Primary Outcome(s)

Safety and dose-limiting toxicity [Time Frame: at 6 weeks]

Secondary Outcome(s)

Progression-free survival [Time Frame: through study completion (5 years)]

Overall survival [Time Frame: through study completion (5 years)]

Radiological response [Time Frame: every 8 weeks until progressive disease or end of study (5 years)]

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)]

Secondary ID(s)

CTU 17.022

Source(s) of Monetary Support

Please refer to primary and secondary sponsors