Ipilimumab for Unresectable stage III–IV melanoma

Inclusion criteria

• {"criterion_text":"- Patient must be of age ≥ 18 years, and have a histologically confirmed diagnosis of locally advanced, surgically incurable, or metastatic cutaneous melanoma.\n- Written and signed informed consent.\n- European Cooperative Oncology Group (ECOG)/World Health Organisation (WHO) performance status of 0 or 1.\n- Patient must be eligible for anti-PD-1 treatment with nivolumab (group 1) or with ipili-mumab + nivolumab (group 2) according to the treating physician.\n- Patient must be eligible for anti-PD-1 treatment with nivolumab (group 1) or with ipili-mumab + nivolumab (group 2) according to the treating physician.\n- Patients must have a life expectancy of 3 months or greater.\n- Patients must have measurable disease (according to RECIST v1.1) with at least one cutaneous metastasis. Note: measurable disease defined as: at least 1 visceral or nodal/soft tissue melanoma lesion that can be accurately and serially measured in at least 1 dimension and for which the longest diameter is ≥ 10 mm as measured by CT-scan or MRI. Lymph nodes must measure ≥ 15 mm in their short axis to be considered measurable by CT-scan or MRI.\n- Adequate bone marrow, hepatic, renal and coagulation function (to be conducted within 7 days prior to start therapy, during the baseline period): o Leukocyte count ≥ 3,5 × 109 / L o Platelets ≥ 100 × 109 / L. o Total bilirubin ≤ 3 × the upper limit of normal (ULN). o Aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) ≤ 3.0 × ULN; except patients with documented liver metastases ASAT and/or ALAT ≤ 5.0 × ULN. o (Estimated) creatinine clearance ≥ 45 mL/min/1,73 m2. o Albumin ≥ 30g / L o LDH ≤ 2 x ULN\n- Women of childbearing potential (WOCBP) must use contraception (see § 9.2.1) during the study and for 23 weeks after the last dose of nivolumab.\n- Men who are sexually active with WOCBP must use contraception (see § 9.2.1) during the study plus 7 months after the last dose of nivolumab."}

Exclusion criteria

• {"criterion_text":"- Primary uveal or mucosal melanoma.\n- Patient has used systemic corticosteroids to treat inflammatory or autoimmune symp-toms within 15 days or other immunosuppressive drugs within 30 days prior to screen-ing. Exceptions: o Patients that require intermittent use of inhalation or topical corticosteroids are eligible for the study. o Patient has received acute, low-dose, systemic immunosuppressant medica-tions (e.g., a one-time dose of dexamethasone for nausea) that, in the opinion of the Investigator, will not compromise protocol objectives.\n- Patient has had treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumour necrosis factor agents) within 2 weeks prior to baseline.\n- Patient has had treatment with systemic immunostimulatory agents (including but not limited to interferons [IFNs] or interleukin-2 [IL-2]) within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to baseline.\n- Known history or evidence of immunodeficiency states (e.g., organ transplant, leukaemia, human immunodeficiency virus (HIV), hepatitis B, hepatitis C or known acquired immunodeficiency syndrome (AIDS)). NOTE: Testing for HIV must be performed at sites were mandated locally.\n- Patient has had any major surgery within 4 weeks prior to enrolment or major surgery is scheduled during the study, with the exception of procedures that are part of the study site IIS.\n- Patient has any safety laboratory test results (clinical chemistry, haematology, and urinalysis) that, in the opinion of the Investigator, could compromise patient safety or protocol objectives.\n- Patient has any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of the ICI treatment, or that may affect the interpretation of the results or render the patient at high risk from complications.\n- Patient has history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanised antibodies or fusion proteins or known allergy to the study IMP ingredients and/or the proposed ICI therapy.\n- Pregnancy or breastfeeding.\n- Patient has a history of alcohol or drug abuse within the last year.\n- Prior treatment with CTLA-4 inhibitor or agonist, or anti-PD1, except for adjuvant nivolumab > 6 months ago.\n- Currently participating in or has participated in a study of an investigational agent within 30 days of baseline or has not recovered from adverse events due to agents adminis-tered more than 4 weeks earlier, except A Phase 1a/1b, Multi-Centre, Open-Label, Dose-Escalation and Dose-Expansion Study in Patients with Solid Tumor Malignancies to Evaluate GEH200520 Injection / GEH200521 (18F) Injection Safety and Tolerability, Positron Emission Tomography Imaging, Pharmacokinetics, and Changes in Imaging after Treatment; NCT05629689, EU Trial number: 2024-515218-42-00.\n- For any reason, patient is considered by the local investigator to be an unsuitable candidate to participate in this study.\n- Prior radiotherapy is permitted except on RECIST v1.1 target lesions within 2 weeks of start of trial treatment. Irradiated lesions without progression before start of treatment cannot be target lesions. Note: Patients must have recovered from all radiation-related toxicities, and not require corticosteroids.\n- Patient has 12-lead ECG significant findings during screening, per Investigator’s assessment.\n- History of another malignancy (that is progressing or requires active treatment) within the previous 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cancer that has undergone potentially curative therapy.\n- Patient has a confirmed active SARS-CoV-2 infection.\n- Patient has serious non-malignant disease or conditions that, in the opinion of the Investigator, could compromise patient safety or protocol objectives.\n- Patient has brain or bone-marrow metastasis that, in the opinion of the Investigator, could compromise patient safety or protocol objectives.\n- Active systemic infections requiring therapy, or signs or symptoms of a systemic infec-tion within two weeks prior to baseline."}

Primary endpoints

• {"endpoint_text":"- T cell subset frequencies (as percentage of parent), and systemic activation (determined as a 50 % or greater increase in expression of inducible T-cell costimulator (ICOS/CD278)) in PBMCs CD4+/CD8+ T cells at baseline and on-treatment in both groups.","definition_or_measurement_approach":"Measured as T cell subset frequencies (percentage of parent) in PBMCs CD4+/CD8+ T cells and systemic activation defined as a ≥50% increase in ICOS (CD278) expression at baseline and on-treatment."}

Secondary endpoints

• {"endpoint_text":"- Safety of i.d. ipilimumab (group 1 only): Adverse events using Common Terminology Criteria Adverse Events, version 5.0 (CTCAE 5.0), reported as frequency of treatment-related events. Grade 3 or higher will be reported separately.","definition_or_measurement_approach":"Safety assessed by frequency of treatment-related adverse events graded per CTCAE v5.0; Grade ≥3 events reported separately."}

Netherlands

Earliest CTIS Part Ii Submission Date

03-03-2026

Latest Decision Or Authorization Date

18-03-2026

Processing Time Days

15

Number Of Sites

1

Number Of Participants

18

Primary sponsor

Full Name

Stichting Amsterdam UMC

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands