Clinical trial · Interventional
Tinostamustine and Nivolumab in Advanced Melanoma
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
NCT03903458CI-TRIAL-00037997ENIgMAunknownPhase 1ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Malignant Melanoma | Melanoma | ALIAS | 0.90 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Tinostamustine | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Tinostamustine and Nivolumab
- description
- Experimental drug combination arm
- interventionNames
- Drug: Tinostamustine
Primary outcomes (1)
- measure
- Safety and dose-limiting toxicity
- timeFrame
- at 6 weeks
- description
- 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
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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
References
Publications (0)
Data not yet available
No reference posted for this study.