Comparing Intravenous or Intradermal Administration of Anti-CTLA-4 in Combination With Anti-PD1 Treatment in Patients With Melanoma

NCT07615881 | Not Yet Recruiting Phase 1

• 2 other identifiers: 2026.03922024-516545-39-00
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Melanoma (Skin Cancer)

Outcome Measures

Primary Outcomes (1)

• Immunological effects

  To determine the systemic immunological effects of standard i.v nivolumab combined with a single dose of 20 mg ipilimumab locally administered i.d. or systemic i.v. administration of standard of care dose ipilimumab as determined with the frequency and functionality of CD4+ and CD8+ T cells in peripheral blood cells.

  13 weeks

Study Arms (2)

Group 1 - Intradermal ipilimumab

EXPERIMENTAL

Patients with advanced/metastatic melanoma who are eligible for standard of care i.v nivolumab will be treated by a single local i.d. injection of 20 mg ipilimumab around (the exci sion site of the) primary tumour or around a skin metastasis, in combination with treatment with i.v. nivolumab continuous.

Drug: Group 1 - Intradermal ipilimumab

Group 2 - Conventional treatment

ACTIVE COMPARATOR

Patients with advanced advanced/metastatic melanoma who are eligible for standard for standard of care i.v. ipilimumab (4 cycles) combined with i.v. nivolumab (continuous) will be treated accordingly.

Drug: Group 2 - Conventional treatment

Interventions

Group 1 - Intradermal ipilimumab DRUG

Patients will be treated once by local i.d. injection of 20 mg ipilimumab around (the excision site of the) primary tumour or around a skin metastasis, in combination with i.v. nivolumab according to standard of care (continuous).

Group 1 - Intradermal ipilimumab

Group 2 - Conventional treatment DRUG

Patients will be treated according to standard of care with i.v. ipilimumab (4 cycles) combined with i.v. nivolumab (continuous).

Group 2 - Conventional treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Primary uveal or mucosal melanoma.
• 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.
• Patient has 12-lead ECG significant findings during screening, per Investigator's as sessment.
• 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.
• Patient has brain or bone-marrow metastasis that, in the opinion of the Investigator, could compromise patient safety or protocol objectives.
• 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.
• 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.

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead
• GE Healthcare: collaborator

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor, Medical Oncology, Medical Specialist, Internal Medicine

Study Record Dates

• First Submitted: May 22, 2026
• First Posted: May 29, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2029
• Last Updated: May 29, 2026

Record last verified: 2026-05