NCT07436390

IFN-Gamma Expression as a Predictor of Response to Immune Checkpoint Inhibitors in First-Line Metastatic Melanoma

IFN-Gamma Expression in Tumor Tissue and Blood as a Predictor of Response to Immune Checkpoint Inhibitors in the First-Line Treatment of Metastatic Melanoma

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 132 (actual)
• Sponsor: Institute of Oncology Ljubljana · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study evaluates whether interferon-gamma (IFN-γ) expression in tumor tissue and peripheral blood can serve as a predictive biomarker of response to immune checkpoint inhibitors in the first-line treatment of metastatic melanoma. Although immune checkpoint inhibitors have substantially improved outcomes in metastatic melanoma, not all patients respond to therapy. Reliable biomarkers that could help identify patients most likely to benefit from treatment are still lacking. This study investigates the association between IFN-γ expression levels and objective treatment response. In addition, the study explores whether characteristics of the gut microbiome are associated with immunotherapy outcomes. The results may contribute to improved patient stratification and personalized treatment approaches in metastatic melanoma.

Detailed description

Immune checkpoint inhibitors have significantly improved survival in patients with metastatic melanoma. However, treatment response varies considerably, and a substantial proportion of patients do not achieve durable benefit. The identification of predictive biomarkers remains an important unmet clinical need. This prospective, single-arm interventional study evaluates biological markers in patients receiving first-line immune checkpoint inhibitor therapy for metastatic melanoma. The primary objective is to assess whether interferon-gamma (IFN-γ) expression in tumor tissue and peripheral blood is associated with objective response to treatment. Tumor IFN-γ expression is assessed using immunohistochemistry, and peripheral blood IFN-γ concentration is measured using enzyme-linked immunosorbent assay (ELISA). The study also evaluates additional biomarkers, including PD-L1 expression, to explore their potential predictive value. Furthermore, the study investigates the relationship between gut microbiome composition and treatment outcomes. Microbiome diversity and bacterial taxonomic profiles are analyzed from stool samples to determine whether microbial characteristics are associated with response to immunotherapy. The study is conducted at a single tertiary oncology center and includes adult patients with metastatic melanoma receiving standard-of-care first-line immune checkpoint inhibitor therapy. The findings aim to support improved risk stratification and biomarker-guided therapeutic decision-making.

Conditions

• Metastatic Melanoma
• Malignant Melanoma
• Skin Cancer

Interventions

Type	Name	Description
DRUG	Pembrolizumab	PD-1 inhibitor used as first-line immunotherapy in patients with metastatic malignant melanoma.
DRUG	Nivolumab	PD-1 inhibitor used as first-line immunotherapy in patients with metastatic malignant melanoma.
DRUG	Ipilimumab/Nivolumab	Combination immunotherapy with PD-1 inhibitor (nivolumab) and CTLA-4 inhibitor (ipilimumab) used as first-line treatment in metastatic malignant melanoma.

Timeline

• Start date: 2024-03-31
• Primary completion: 2024-03-31
• Completion: 2024-03-31
• First posted: 2026-02-27
• Last updated: 2026-03-02

Locations

1 site across 1 country: Slovenia