Expression of IL4 Induced Gene 1 in Patients With Cutaneous Melanoma: Value in Prognosis and/or in Predictive Response to Immune Checkpoint Inhibitors (ENZYMELA)

May 18, 2026 updated by: Assistance Publique - Hôpitaux de Paris

Impact of the IL4I1 Enzyme Expression in Patients With Cutaneous Melanoma: Prognostic Value and/or Role in Resistance to Current Immunotherapy and Targeted Therapy

To characterize and quantify immune cells expressing the Interleukine 4 induced gene 1 (IL4I1) immunosuppressive enzyme in the blood and in tissue of melanoma patients (primary tumor, sentinel lymph nodes and cutaneous metastases).

Then, to compare the results obtained in different clinical settings:

  • in cases of progression of the disease slower or faster compared to the prognosis established by clinical and pathological data
  • before and after treatments with immunotherapy (anti Programmed Death ligand 1 (anti-PD1) or anti-PD1 and anti Cytotoxic T Lymphocyte associated protein 4 (anti-CTLA-4)) and / or targeted therapies (BRAF inhibitors and /or methyl ethyl ketone (MEK)).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The incidence of cutaneous melanoma is increasing, but the current prognostic parameters mainly based on histological data are insufficient to identify patients with high risk of recidive. In addition, current immunotherapies using PD-1 and/or CTLA-4 antibodies have long-lasting tumor control in a substantial fraction of patients but identify new markers of treatment resistance need further investigations. Clinical data highlight enzymes involved in amino acid catabolism as new potential prognostic markers in human melanoma. Among those, the IL4I1 phenylalanine oxidase may be a new relevant marker and may represent an easily targetable molecule for cancer immunotherapy.

The current retrospective study is designed to evaluate whether a high proportion of IL4I1 positive cells within the primary tumor and/or sentinel lymph nodes allows to predict the risk of cancer recurrence from the clinical diagnosis. Immunofluorescence and immunohistochemistry will be performed.

The longitudinal study of IL4I1 positive cells in the blood and cutaneous metastasis od patients will start before and after (three months and 1 year (or before in case of treatment resistance) the treatment with targeted therapy and/or immunotherapy as a first line. Treatment will be administered on an outpatient basis. No investigational or commercial cancer directed agents or therapies other than those described below may be administered.

It is designed to evaluate whether patients that resist to treatments exhibit a high proportion of IL4I1 positive cells and how is regulated the enzyme in the course of the treatment.

Study Type

Interventional

Enrollment (Actual)

127

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
    • Île-de-France Region
      • Paris, Île-de-France Region, France, 75014
        • Dermatology department

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • group 1: patients with primary thin melanoma (Breslow thickness less than or equal to1 mm) monitored for 10 years, having relapsed or not within 10 years after the diagnosis.

    • patients with no other concomitant cancers requiring systemic treatment at the time of diagnosis of primary melanoma
    • patient or patient's family (in case of death) informed of the objectives and modalities of the study and not opposed to participation in the study
    • patient or patient's family (in case of death) not opposed to the use of part of the skin sample previously taken for the present research

  • group 2: patients with primary thick melanoma (Breslow greater than or equal to 3 mm) monitored for 5 years, having relapsed or not within 5 years after diagnosis.

    • patient with no other concomitant cancers requiring systemic treatment at the time of diagnosis of primary melanoma
    • patient or patient's family (in case of death) informed of the objectives and modalities of the study and not opposed to participation in the study
    • patient or patient's family (in case of death) not opposed to the use of part of the skin sample previously taken for the present research

  • group 3: patient with melanoma (stages III or IV inoperable) and who are treated with immunotherapy and / or biotherapy

    • patient with no other concomitant cancers requiring systemic treatment at the time of diagnosis of primary melanoma and initiation of systemic treatment for melanoma
    • patient informed of the objectives and modalities of the study and having given informed and written consent to participate in the study

Exclusion Criteria:

  • groups 1 and 2: patient or family of the patient opposed (e) that part of the primary melanoma taken previously is used in the context of the present project

  • group 3 :

    • refusal of the patient to participate in the study
    • patient unable to understand the study and sign consent
    • patient with a known contraindication to xylocaine
    • patient not affiliated to a social security system (beneficiary or beneficiary's right)
    • adult subject to a legal protection measure

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: patients with primary thin melanoma < or = 1mm
patients with primary thin melanoma (Breslow thickness less than or equal 1 mm)
No Intervention: patients with primary thick melanoma > or = 3 mm
patients with primary thick melanoma (Breslow greater than or equal 3 mm)
Other: patient with melanoma who received treatment
patient with melanoma (stages III or IV inoperable) and who received first line treatment with immunotherapy and / or targeted therapies
Biological: Blood sample
Blood sample before treatment, 3 months after treatment and after 1 year or relapse or resumption of disease progression.
Biological: Cutaneous melanoma biopsy
Cutaneous melanoma biopsy before treatment, 3 months after treatment and relapse or resumption of disease progression.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Role of IL4I1+ cells in prognosis and in response to treatments (targeted and/or antiPD1/CTLA4 based therapies) in cutaneous melanoma
Time Frame: 12 months or between 6 and 12 months (if disease progression)
Detection of IL4I1+ cells in tissue and/or blood
12 months or between 6 and 12 months (if disease progression)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

Institut National de la Santé Et de la Recherche Médicale, France
Société de Dermatologie Française
URC-CIC Paris Descartes Necker Cochin
Institut Cochin
Association Robert Debré (ARD)

Investigators

  • Principal Investigator: Armelle Blondel, MD, PhD, Institut National de la Santé Et de la Recherche Médicale, France

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 12, 2022

Primary Completion (Actual)

November 4, 2024

Study Completion (Actual)

November 4, 2024

Study Registration Dates

First Submitted

January 31, 2020

First Submitted That Met QC Criteria

January 31, 2020

First Posted (Actual)

February 5, 2020

Study Record Updates

Last Update Posted (Actual)

May 20, 2026

Last Update Submitted That Met QC Criteria

May 18, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APHP190243
  • 2019-A01985-52 (Registry Identifier: ID-RCB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The clinical data at the diagnosis and the relapse/no relapse information have to be shared from the groups 1 and 2.

The clinical response to treatments will be shared.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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