Immunological Functionnal Test Validation to Predict Melanoma Metastatic Patient Response to Checkpoint Inhibitors (mela-quantif)

Centre Hospitalier Universitaire de Nice

Status: Enrolling

Conditions: Melanoma (Skin)

Treatments: Biological: Evaluation of cytokine production

Study type: Interventional

Funder types: Other

Identifiers

NCT05649683

22-PP-14

Details and patient eligibility

About

Checkpoint inhibitor such as anti-CTLA-4 and anti-PD-1 are known to block inhibitory signals and increase the immune antimutoral response. Nivolumab and Ipilimumab association is considered as a more efficient immunotherapy to treat advanced melanoma. This combined immunotherapy is also responsible of severe immunes toxicyties. Identification of predictives biomarqueurs remains a challenge to predict the balance between tolerability and efficency. Previous data showed that advanced melanoma patient had lower level of Th1 cytokines that predict a less efficient immune system than healthy donors. The second point was that high level of Th1 and Th17 cytokines were correlate to a better tumor response. The last point was that patients with severe immune toxicity showed an increase of IL-6 and IL17a production. The investigators would like to identify the predictive values of Th1, Th2 and Th17 at the begining and during the combined immunotherapy and correlate these cytokines levels secretions to a potential efficient tumor response or to the emergence of induced immunes toxicities. This study is an original approach using functionnal test to predict the balance between efficienty and tolerability.

Enrollment: 60 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion

• persone of major age,
• advanced melanoma confirmed,
• RECIST 1.1 disease,
• first line treatment

Exclusion Criteria:

• occular and mucosal melanoma,
• previous checkpoint inhibitor treatment,
• active brain metastasis,
• concomitant immunosuppressive treatment

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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60 participants in 1 patient group

Analysis of blood cytokine

Other group

Description:

Patients will receive anti-PD1 therapy (Nivolumab/Nivo) with anti-CTLA4 therapy (Ipilimumab/Ipi) as part of routine care, as per the MA scheme followed in case of efficacy and good tolerance of Nivolumab maintenance treatment alone. The functional test for cytokines (1ml total blood on lihtium heparinate) will be performed at the initiation of ICI (J0), at week 6 (S6, after the 2nd cure), at week 11 (S11= 1st radiological evaluation, after the 4 cures of Nivo+Ipi), and, if applicable, the progression of the disease and/or the occurrence of an ESi grade 3-4. Stimulated lymphocytes from non-therapy responders will be tested in vitro by various immunomodulatory drugs. During each sampling we will also collect 5 ml of serum on dry tube for serological constitution, 3ml on EDTA tube for performing an immunophenotyping (T, B, NK) and 3ml on EDTA tube for freezing total PBMC and setting up a biobank.

Treatment:

Biological: Evaluation of cytokine production