Metastatic MelanomaMAKNCT07436390
IFN-Gamma Expression as a Predictor of Response to Immune Checkpoint Inhibitors in First-Line Metastatic Melanoma
A study testing Pembrolizumab, Nivolumab and Ipilimumab/Nivolumab in people with Metastatic Melanoma and Malignant Melanoma, run by Institute of Oncology Ljubljana at 1 site in Slovenia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma, Malignant Melanoma, Skin Cancer
- What is being tested?
- Pembrolizumab, Nivolumab and Ipilimumab/Nivolumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 132 participants
- Where
- 1 siteSlovenia
- Study dates
- 31 Mar 2024to 31 Mar 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
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.
Read the 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
- Being tested
- Pembrolizumab, Nivolumab, Ipilimumab/Nivolumab
- Keywords
- Immunotherapy, Immune Checkpoint Inhibitors
- Medical subject headings
- Melanoma, Skin Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
PD-1 inhibitor used as first-line immunotherapy in patients with metastatic malignant melanoma.
NivolumabDrug
PD-1 inhibitor used as first-line immunotherapy in patients with metastatic malignant melanoma.
Ipilimumab/NivolumabDrug
Combination immunotherapy with PD-1 inhibitor (nivolumab) and CTLA-4 inhibitor (ipilimumab) used as first-line treatment in metastatic malignant melanoma.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Pembrolizumab; Drug: Nivolumab; Drug: Ipilimumab/Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 28 weeks after treatment initiation
Secondary outcomes (4)
Tumor Tissue IFN-Gamma Expression Assessed by Immunohistochemistry (IHC)
Interferon-gamma (IFN-γ) expression in tumor tissue measured using immunohistochemistry (IHC). Expression will be quantified using the Histochemical Score (H-score), a semi-quantitative scoring system ranging from 0 to 300. Higher H-scores indicate higher IFN-γ expression levels in tumor tissue.
Measured: Baseline (within 4 weeks before treatment initiation)
Peripheral Blood IFN-Gamma Concentration Measured by ELISA
Interferon-gamma (IFN-γ) concentration in peripheral blood measured using enzyme-linked immunosorbent assay (ELISA) and reported in picograms per milliliter (pg/mL).
Measured: Baseline and up to 28 weeks after treatment initiation
Gut Microbiome Alpha Diversity Index Assessed by 16S rRNA Sequencing
Gut microbiome diversity assessed from stool samples using 16S rRNA sequencing. Alpha diversity will be quantified using the Shannon diversity index.
Measured: Baseline (up to 4 weeks before treatment initiation)
Relative Abundance of Bacterial Taxa in Stool Samples Assessed by 16S rRNA Sequencing
Relative abundance (%) of bacterial taxa assessed from stool samples using 16S rRNA sequencing.
Measured: Baseline (up to 4 weeks before treatment initiation)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2026
- Study start31 Mar 2024
- Primary completion31 Mar 2024
- Study completion31 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 132 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institute of Oncology Ljubljana
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07436390
- Sponsor's protocol ID
- ERIDSPRA-0028/2022
- Other IDs
- ERIDSPRA-0028/2022
- Acronym
- MAK
- Status last verified
- Feb 2026
- First submitted
- 5 Feb 2026
- Last updated
- 2 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07436390
- Acronym / sponsor ID
- MAK / ERIDSPRA-0028/2022
- Conditions
- Metastatic Melanoma, Malignant Melanoma, Skin Cancer
- Keywords
- Immunotherapy, Immune Checkpoint Inhibitors
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 132 participants (actual)
- Lead sponsor
- Institute of Oncology LjubljanaUniversity, hospital or other
- Study start
- 31 Mar 2024 (actual)
- Primary completion
- 31 Mar 2024 (actual)
- Study completion
- 31 Mar 2024 (actual)
- First posted
- 27 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Immune Checkpoint Inhibitor Therapy | Other | Drug: Pembrolizumab, Drug: Nivolumab, Drug: Ipilimumab/NivolumabPatients 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (4 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabPD-1 inhibitor used as first-line immunotherapy in patients with metastatic malignant melanoma. | Drug | Immune Checkpoint Inhibitor Therapy |
| NivolumabPD-1 inhibitor used as first-line immunotherapy in patients with metastatic malignant melanoma. | Drug | Immune Checkpoint Inhibitor Therapy |
| Ipilimumab/NivolumabCombination immunotherapy with PD-1 inhibitor (nivolumab) and CTLA-4 inhibitor (ipilimumab) used as first-line treatment in metastatic malignant melanoma. | Drug | Immune Checkpoint Inhibitor Therapy |
Primary outcome
Objective Response Rate (ORR) Assessed by Immune-Related RECIST (irRECIST)
Time frame: Up to 28 weeks after treatment initiation
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.
4 secondary outcomes
Tumor Tissue IFN-Gamma Expression Assessed by Immunohistochemistry (IHC)
Time frame: Baseline (within 4 weeks before treatment initiation)
Peripheral Blood IFN-Gamma Concentration Measured by ELISA
Time frame: Baseline and up to 28 weeks after treatment initiation
Gut Microbiome Alpha Diversity Index Assessed by 16S rRNA Sequencing
Time frame: Baseline (up to 4 weeks before treatment initiation)
Relative Abundance of Bacterial Taxa in Stool Samples Assessed by 16S rRNA Sequencing
Time frame: Baseline (up to 4 weeks before treatment initiation)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2026.
- Individual participant dataSharing planned: No
Related trials for Metastatic Melanoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
RecruitingPhase 3
A Study With Combinations of Anti-LAG-3 and Anti-PD-1 Antibodies in Adult Participants With Advanced or Metastatic Melanoma (Harmony Head-to-Head)
Melanoma
RecruitingPhase 1
Pharmacokinetics, Safety, and Immunogenicity Comparison of Bmab1700 and Opdivo® as Adjuvant Monotherapy in Participants With Melanoma
Melanoma
Active, not recruitingPhase 1/2
A Study of ST-1898 for Unresectable or Metastatic Melanoma
Unresectable or Metastatic Melanoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pembrolizumab, Nivolumab and Ipilimumab/Nivolumab in people with Metastatic Melanoma and Malignant Melanoma, run by Institute of Oncology Ljubljana at 1 site in Slovenia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Slovenia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) Assessed by Immune-Related RECIST (irRECIST) (time frame: Up to 28 weeks after treatment initiation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2026.