NCT07428252

Brief Summary

The aim of this prospective clinical study is to evaluate the prognostic and predictive significance of the gastrointestinal microbiome in patients with metastatic malignant melanoma treated with first-line immunotherapy using immune checkpoint inhibitors (PD-1 inhibitors and CTLA-4 inhibitors). Although immunotherapy has significantly improved survival outcomes, treatment response remains unpredictable and a substantial proportion of patients develop immune-related adverse events, pseudoprogression, or hyperprogression. The gastrointestinal microbiome is an important regulator of immune homeostasis and may influence systemic immune response. This study investigates whether specific microbiome composition is associated with objective treatment response assessed according to iRECIST criteria, progression-free survival (PFS), and the occurrence of immune-related adverse events. Patients treated at the Institute of Oncology Ljubljana between March 2022 and March 2024 were enrolled. In addition to standard-of-care immunotherapy, participants underwent protocol-defined collection of stool and peripheral blood samples at predefined time points for microbiome and immune profiling analyses.

Trial Health

55
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
150

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Mar 2022

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2022

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 31, 2024

Completed
1.9 years until next milestone

First Submitted

Initial submission to the registry

February 5, 2026

Completed
18 days until next milestone

First Posted

Study publicly available on registry

February 23, 2026

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

March 31, 2026

Completed
Last Updated

February 25, 2026

Status Verified

February 1, 2026

Enrollment Period

2.1 years

First QC Date

February 5, 2026

Last Update Submit

February 23, 2026

Conditions

Metastatic Malignant Melanoma

Keywords

Metastatic melanomaImmunotherapy

Outcome Measures

Primary Outcomes (1)

  • Objective Treatment Response According to irRECIST

    Treatment response evaluated radiologically using PET/CT or CT triplet and assessed according to irRECIST criteria (CR, PR, SD, PD).

    Baseline (within 4 weeks before treatment initiation) and up to 28 weeks (+2 weeks) after treatment initiation

Secondary Outcomes (2)

  • Progression-Free Survival (PFS)

    From treatment initiation up to 24 months

  • Immune-Related Adverse Events

    From treatment initiation up to 24 months

Study Arms (2)

PD-1 inhibitor therapy

OTHER

Patients with metastatic malignant melanoma treated in the first line with PD-1 inhibitors (pembrolizumab or nivolumab).

Drug: PD-1 and CTLA-4 inhibitors

Combination PD-1 and CTLA-4 inhibitor therapy

OTHER

Patients with metastatic malignant melanoma treated in the first line with combined immunotherapy with PD-1 and CTLA-4 inhibitors (ipilimumab/nivolumab).

Drug: PD-1 inhibitors

Interventions

PD-1 inhibitorsDRUG

Pembrolizumab, nivolumab

Combination PD-1 and CTLA-4 inhibitor therapy
PD-1 and CTLA-4 inhibitorsDRUG

Combination immunotherapy ipilimumab/nivolumab

PD-1 inhibitor therapy

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥ 18 years
  • Cytologically or histologically confirmed malignant melanoma
  • Unresectable stage IIID or stage IV disease according to AJCC (8th edition, 2018)
  • ECOG performance status 0-2
  • Indication for first-line systemic immunotherapy (nivolumab, combination ipilimumab/nivolumab, or pembrolizumab)
  • CT or PET/CT imaging performed within 4 weeks prior to first administration of immunotherapy
  • Written informed consent obtained prior to study participation

You may not qualify if:

  • Previous systemic therapy for melanoma
  • ECOG performance status 3-4
  • Contraindications to immunotherapy (e.g., known immunodeficiency, active immunosuppressive treatment, or active autoimmune disease requiring systemic therapy)
  • Presence of another active malignancy, except adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or other solid tumors with no evidence of recurrence for ≥3 years

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Institute of Oncology Ljubljana

Ljubljana, 1000, Slovenia

Location

MeSH Terms

Conditions

Melanoma

Interventions

Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Neuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Nerve TissueNevi and MelanomasSkin NeoplasmsNeoplasms by SiteSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological ActionPharmacologic ActionsChemical Actions and UsesAntineoplastic Agents, ImmunologicalAntineoplastic AgentsTherapeutic Uses

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 5, 2026

First Posted

February 23, 2026

Study Start

March 1, 2022

Primary Completion

March 31, 2024

Study Completion

March 31, 2026

Last Updated

February 25, 2026

Record last verified: 2026-02

Data Sharing

IPD Sharing
Will not share

Locations

SL(1)