Tinostamustine and Nivolumab in Advanced Melanoma (ENIgMA)

Markus Joerger

Status and phase

Unknown

Phase 1

Conditions

Malignant Melanoma

Treatments

Drug: Tinostamustine

Study type

Interventional

Funder types

Other

Identifiers

NCT03903458

CTU 17.022

Details and patient eligibility

About

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.

Full description

Despite improvement of systemic treatment in patients with advanced melanoma, there is still unmet medical need in this group of patients. Tinostamustine is a medication without marketing authorization, while Nivolumab is approved for several tumor entities. The primary objective of this trial is to assesses the safety, tolerability and recommended dose of Tinostamustine in combination with Nivolumab in patients with advanced melanoma.Secondary objectives of this trial in patients with advanced solid tumors are to assess the preliminary efficacy of Tinostamustine when given in combination with Nivolumab and to characterize potential predictive biomarkers of the combination treatment of Tinostamustine and Nivolumab. The trial includeds patients with either histologically or cytologically confirmed inoperable stage III or metastatic stage IV melanoma with an indication for the regular systemic treatment with Nivolumab and a maximum of 1 prior systemic palliative line of treatment.

Enrollment

21 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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).