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.
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.
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.
Parallel
Group 1 - Intradermal ipilimumab
DrugPatients 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 2 - Conventional treatment
DrugPatients will be treated according to standard of care with i.v. ipilimumab (4 cycles) combined with i.v. nivolumab (continuous).
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.
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Amsterdam UMC, location VUmc
Lead sponsor
GE Healthcare
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
