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
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 21
- 试验地点
- 2
- 主要终点
- Safety and dose-limiting toxicity
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
open-label
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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
排除标准
- •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
研究组 & 干预措施
Tinostamustine and Nivolumab
Experimental drug combination arm
干预措施: Tinostamustine (Drug)
结局指标
主要结局
Safety and dose-limiting toxicity
时间窗: at 6 weeks
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
次要结局
- Overall safety profile of the tinostamustine/nivolumab drug combination(during a maximum 2 years of study treatment plus 100 days thereafter (3 years))
- Radiological response(every 8 weeks until progressive disease or end of study (5 years))
- Progression-free survival(through study completion (5 years))
- Overall survival(through study completion (5 years))
研究者
Markus Joerger
Chair Clinical Research Unit
Cantonal Hospital of St. Gallen