Metastatic Melanoma, Skin Cancer
Conditions
Keywords
Immunotherapy, Immune Checkpoint Inhibitors
Brief summary
The purpose of this study is to evaluate the efficacy of immunotherapy in the first-line treatment of metastatic melanoma in Slovenia and to investigate the association between PD-L1 expression and treatment response. The study aims to determine the relationship between exosomal PD-L1 miRNA expression, PD-L1 expression in tumor tissue, and PD-L1 expression on the surface of immune cells, and response to immunotherapy. The study will also evaluate the association between immune-related adverse events and survival.
Detailed description
This study evaluates the efficacy of immunotherapy in the first-line treatment of metastatic melanoma in Slovenia and investigates the predictive value of PD-L1 expression in tumor tissue and blood. The aim is to assess the association between exosomal PD-L1 miRNA expression, PD-L1 expression in tumor tissue, and PD-L1 expression on the surface of immune cells, and response to treatment with immune checkpoint inhibitors. In addition, the study evaluates the association between the occurrence of immune-related adverse events and survival.
Interventions
DRUGPembrolizumab
PD-1 immune checkpoint inhibitor administered as first-line therapy according to standard clinical practice.
DRUGNivolumab
Nivolumab is a PD-1 immune checkpoint inhibitor administered as first-line systemic immunotherapy for metastatic malignant melanoma according to standard clinical practice, either as monotherapy or in combination with ipilimumab.
DRUGIpilimumab
Ipilimumab is a CTLA-4 immune checkpoint inhibitor administered in combination with nivolumab as first-line systemic immunotherapy for metastatic malignant melanoma according to standard clinical practice.
Sponsors
Institute of Oncology Ljubljana
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Non-randomized comparative study evaluating response to immune checkpoint inhibitors in first-line treatment of metastatic melanoma and association with PD-L1 expression in tumor tissue and blood.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years * Cytologically or histologically confirmed metastatic malignant melanoma * Stage IIID unresectable or stage IV (AJCC 8th edition) * ECOG performance status 0-2 * First-line systemic immunotherapy (pembrolizumab, nivolumab, or ipilimumab/nivolumab) * CT/PET-CT performed within 4 weeks prior to treatment start * Signed informed consent
Exclusion criteria
* Previous systemic therapy for melanoma * ECOG performance status 3-4 * Contraindications to immunotherapy (immune deficiency, active immunosuppressive therapy, or active autoimmune disease requiring systemic treatment) * Other active malignancy (except cured basal cell carcinoma, squamous cell carcinoma, or other solid tumors without recurrence \>3 years)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) According to irRECIST | Baseline; Week 12 (±2 weeks); Week 28 (±2 weeks) | Objective response will be assessed using CT or PET/CT imaging and evaluated according to irRECIST criteria. The outcome will be reported as the proportion (%) of participants achieving complete response (CR) or partial response (PR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PD-L1 Expression in Tumor Tissue (Immunohistochemistry, H-score or % Positive Cells) | Baseline | PD-L1 expression in tumor tissue will be assessed using immunohistochemistry (IHC). The outcome will be reported as PD-L1 expression level (H-score and/or percentage of PD-L1 positive tumor cells) and correlated with objective response according to irRECIST. |
Countries
Slovenia
Contacts
CONTACTTanja Mesti, MD
Outcome results
None listed