Ipilimumab Given Into the Skin or Into a Vein With Nivolumab for Advanced Melanoma

Trial details

Who runs it

Amsterdam UMC, location VUmc

Trial code

NCT07615881EU 2024-516545-39-01

Record updated

29 May 2026

Original description

This study investigates whether a single intradermal (i.d.) injection of low-dose anti-CTLA-4 (ipilimumab), given at the tumour site, can enhance immune activation when combined with standard intravenous (i.v.) anti-PD-1 therapy in patients with advanced melanoma. While combined checkpoint inhibition is effective, it is associated with high toxicity, creating a need for strategies that maintain efficacy with fewer side effects.Read full original descriptionShow less

Changes in the Tumour Microenvironment After Intravenous or Intradermal Administration of Anti-CTLA-4 in Combination With Anti-PD1 Treatment in Patients With Melanoma

This study investigates whether a single intradermal (i.d.) injection of low-dose anti-CTLA-4 (ipilimumab), given at the tumour site, can enhance immune activation when combined with standard intravenous (i.v.) anti-PD-1 therapy in patients with advanced melanoma. While combined checkpoint inhibition is effective, it is associated with high toxicity, creating a need for strategies that maintain efficacy with fewer side effects.

Preclinical and early clinical data suggest that local (intradermal) CTLA-4 blockade can stimulate systemic anti-tumour immune responses with reduced toxicity, potentially by reactivating suppressed T cells in tumour-draining lymph nodes. This study compares systemic immune effects of intradermal versus standard intravenous CTLA-4 administration, both combined with nivolumab.

The primary objective is to assess systemic immune activation by measuring changes in CD4+ and CD8+ T-cell frequencies and ICOS expression in peripheral blood. Additional immune monitoring includes blood sampling, tumour biopsies, and advanced imaging using FDG-PET/CT and a novel CD8-targeted PET tracer. The study is a prospective, open-label pilot trial in patients with metastatic melanoma, with follow-up for clinical outcomes and immune response over approximately 13 weeks.

Inclusion: Patient must be of age ≥ 18 years, and have a histologically confirmed diagnosis of locally advanced, surgically incurable, or metastatic cutaneous melanoma; European Cooperative Oncology Group (ECOG)/World Health Organisation (WHO) performance status of 0 or 1; Patient must be eligible for anti-PD-1 treatment with nivolumab (group 1) or with ipilimumab + nivolumab (group 2) according to the treating physician; Patient must have one or more tumour lesions of which a biopsy can safely be obtained according to standard clinical practice; Patients must have a life expectancy of 3 months or greater; 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; Adequate bone marrow, hepatic, renal and coagulation function (to be conducted within 7 days prior to start therapy, during the baseline period):; Leukocyte count ≥ 3,5 × 109 / L; Platelets ≥ 100 × 109 / L; Total bilirubin ≤ 3 × the upper limit of normal (ULN); ASAT and ALAT ≤ 3.0 × ULN; except patients with documented liver metastases ASAT and/or ALAT ≤ 5.0 × ULN; (Estimated) creatinine clearance ≥ 45 mL/min/1,73 m2; Albumin ≥ 30g / L; LDH ≤ 2 x ULN; Women of childbearing potential (WOCBP) must use contraception during the study and for 23 weeks after the last dose of nivolumab; Men who are sexually active with WOCBP must use contraception during the study plus 7 months after the last dose of nivolumab; Written and signed informed consent.

Exclusion: Prior treatment with CTLA-4 inhibitor or agonist, or anti-PD1, except for adjuvant nivolumab > 6 months ago; 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; Active systemic infections requiring therapy, or signs or symptoms of a systemic infection within two weeks prior to baseline; Patient has used systemic corticosteroids to treat inflammatory or autoimmune symptoms within 15 days or other immunosuppressive drugs within 30 days prior to screening. Exceptions:; Patients that require intermittent use of inhalation or topical corticosteroids are eligible for the study; Patient has received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) that, in the opinion of the Investigator, will not compromise protocol objectives; 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; 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; 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; 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 administered 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; 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; Patient has a confirmed active SARS-CoV-2 infection; Patient has serious non-malignant disease or conditions that, in the opinion of the Investigator, could compromise patient safety or protocol objectives; 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; 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; Patient has a history of alcohol or drug abuse within the last year; 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; 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; Primary uveal or mucosal melanoma; Patient has 12-lead ECG significant findings during screening, per Investigator's as sessment; Patient has brain or bone-marrow metastasis that, in the opinion of the Investigator, could compromise patient safety or protocol objectives; Pregnancy or breastfeeding; For any reason, patient is considered by the local investigator to be an unsuitable candidate to participate in this study.

ClinicalTrials.gov NCT07615881 · EU CTIS 2024-516545-39-01