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

NCT07436390 | Completed

• 1 other identifier: ERIDSPRA-0028/2022
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Metastatic Melanoma; Malignant Melanoma; Skin Cancer

Keywords

Immunotherapy; Immune Checkpoint Inhibitors

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) Assessed by Immune-Related RECIST (irRECIST)

  Objective response rate defined as the proportion of participants achieving complete response (CR) or partial response (PR) according to immune-related Response Evaluation Criteria in Solid Tumors (irRECIST), based on CT or PET/CT imaging assessment.

  Up to 28 weeks after treatment initiation

Secondary Outcomes (4)

• Tumor Tissue IFN-Gamma Expression Assessed by Immunohistochemistry (IHC)

  Baseline (within 4 weeks before treatment initiation)

• Peripheral Blood IFN-Gamma Concentration Measured by ELISA

  Baseline and up to 28 weeks after treatment initiation

• Gut Microbiome Alpha Diversity Index Assessed by 16S rRNA Sequencing

  Baseline (up to 4 weeks before treatment initiation)

• Relative Abundance of Bacterial Taxa in Stool Samples Assessed by 16S rRNA Sequencing

  Baseline (up to 4 weeks before treatment initiation)

Study Arms (1)

Immune Checkpoint Inhibitor Therapy

OTHER

Patients with metastatic malignant melanoma will be treated in the first line with immune checkpoint inhibitors: PD-1 inhibitors (pembrolizumab, nivolumab) or combination PD-1 and CTLA-4 inhibitors (ipilimumab/nivolumab).

Drug: Pembrolizumab; Drug: Nivolumab; Drug: Ipilimumab/Nivolumab

Interventions

Pembrolizumab DRUG

PD-1 inhibitor used as first-line immunotherapy in patients with metastatic malignant melanoma.

Immune Checkpoint Inhibitor Therapy

Nivolumab DRUG

PD-1 inhibitor used as first-line immunotherapy in patients with metastatic malignant melanoma.

Immune Checkpoint Inhibitor Therapy

Ipilimumab/Nivolumab DRUG

Combination immunotherapy with PD-1 inhibitor (nivolumab) and CTLA-4 inhibitor (ipilimumab) used as first-line treatment in metastatic malignant melanoma.

Immune Checkpoint Inhibitor Therapy

Eligibility Criteria

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

You may qualify if:

• Age over 18 years
• Cytologically or histologically verified malignant melanoma
• Stage IIID unresectable/IV according to AJCC classification (8th edition, 2018)
• Performance status WHO 0-2 (ECOG criteria)
• First-line systemic immunotherapy treatment (nivolumab, ipilimumab/nivolumab combination, pembrolizumab)
• CT triple scan/PET CT performed within 4 weeks prior to the first administration
• Signed informed consent for participation in the clinical study

You may not qualify if:

• Previous systemic therapy for melanoma
• Performance status WHO 3-4 (ECOG criteria)
• Contraindications for immunotherapy (known immune deficiency, active immunosuppressive treatment, or active autoimmune disease requiring treatment)
• Other malignant diseases (except cured basal cell carcinoma, squamous cell carcinoma, and other cured solid tumors without recurrence more than three years after treatment)

Sponsors & Collaborators

• Institute of Oncology Ljubljana: lead

Study Sites (1)

Institute of Oncology Ljubljana

Ljubljana, 1000, Slovenia

Location

MeSH Terms

Conditions

Melanoma; Skin Neoplasms

Interventions

pembrolizumab; Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single-arm interventional study in which all enrolled participants receive standard-of-care first-line immune checkpoint inhibitor therapy for metastatic melanoma. The study evaluates biomarker expression and its association with treatment response without randomization or treatment allocation.

Study Record Dates

• First Submitted: February 5, 2026
• First Posted: February 27, 2026
• Study Start: March 31, 2024
• Primary Completion: March 31, 2024
• Study Completion: March 31, 2024
• Last Updated: March 2, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

SL (1)