Immunotherapy With Nivolumab or Nivolumab Plus Ipilimumab vs. Double Placebo for Stage IV Melanoma w. NED

This is an interventional treatment trial for Malignant Melanoma Read More

Inclusion Criteria:

• Stage IV melanoma arising from a primary cutaneous site or metastatic from an unknown primary site with no evidence of disease (NED) after surgery or radiation therapy (conducted within 8 weeks before enrolment)
• Signed written informed consent
• Known BRAF status
• Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study
• Minimum life expectancy of five years excluding their melanoma diagnosis
• ECOG performance status of 0 or 1
• Tumor tissue from the resected site of disease must be provided for biomarker analyses. In order to be randomized a subject must have a PD-L 1 expression classification (positive (≥ 5% tumor cells expressing PD-L1) or negative (< 5% tumor cells expressing PD-L1)). If an insufficient amount of tumor tissue from the resected site is provided for analysis, acquisition of additional archived tumor tissue (block and/or slides) for the biomarker analyses is required.
• Prior radiotherapy must have been completed at least 2 weeks prior to study drug administration
• Required laboratory values
• Negative pregnancy test for female subjects and effective contraception (Pearl-Index <1) for both male and female subjects if the risk of conception exists

Exclusion Criteria:

• History of primary uveal or mucosal melanoma
• Prior therapy with CTLA4 or PD1 antibodies
• The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the trial procedures.
• Lack of availability for clinical follow-up assessments.
• Any immunosuppressive therapy given within the past 30 days prior to study drug administration (excluding physiologic steroid hormone replacement)
• Other malignancies within the past five years requiring treatment except basal or squamous skin carcinomas or carcinoma in situ of the cervix
• Serious cardiac, gastrointestinal, hepatic or pulmonary disease reducing life expectancy to less than five years
• Patients with serious intercurrent illness, requiring hospitalization.
• Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding disorders.
• The patient is known to be positive for Human Immunodeficiency Virus (HIV) or other chronic infections (HBV, HCV) or has another confirmed or suspected immunosuppressive or immunodeficient condition.
• Known hypersensitivity reaction to any of the components of study treatment
• Pregnancy (absence to be confirmed by ß-HCG urinary test, minimum sensitivity 25IU/L or equivalent units of HCG)) or lactation period
• Women of childbearing potential (WOCBP): Refusal or inability to use effective means of contraception (Pearl-Index <1). WOCBP will be instructed to adhere to contraception until 31 weeks after the last dose of investigational product
• Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year (Pearl-Index <1). Men receiving Nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception until 31 weeks after the last dose of investigational product
• Known alcohol or drug abuse
• Participation in another clinical study and use of any investigational or non-registered product (drug or vaccine) within the 30 days before registration
• Significant disease or condition which, in the investigator's opinion, would exclude the patient from the study
• Legal incapacity or limited legal capacity