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ClinicalTrials.gov ID

NCT07376512

Lead Sponsor

Centre Georges Francois LeclercOTHER

Overall Status

Not yet recruiting

Study Type

Observational

Enrollment

378Estimated

Last Update Posted

Jan 29, 2026Actual

Start Date

Mar 1, 2026Estimated

Primary Completion Date

Mar 1, 2029Estimated

Completion Date

Mar 1, 2030Estimated

Official Title

Predicting Response to Anti-PD-1/PD-L1 Immunotherapy by Plasma Extracellular Vesicle Analysis

Brief Summary

The objective of this prospective multicenter study is to evaluate whether the analysis of immunological biomarkers present in circulating extracellular vesicles is associated with the response to anti-PD-1/PD-L1 treatments in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) or unresectable melanoma.

Patients will receive standard-of-care treatment and will be followed according to routine clinical practice. The study involves the collection of four study-specific blood samples at different time points during follow-up, as well as the collection of standard immunohistochemistry results, thoraco-abdomino-pelvic CT scans, and tumor DNA genotyping analyses performed as part of routine care.

The study aims to determine:

• whether baseline biomarkers in extracellular vesicles are associated with response to anti-PD-1/PD-L1 treatment,
• how these biomarkers change over the course of treatment, and
• to provide exploratory data for the development of predictive immunological response signatures.

Detailed Description

Immune checkpoint inhibitors (anti-PD-1/PD-L1) have become standard treatment for patients with advanced or metastatic non-small cell lung cancer (NSCLC) or melanoma. However, not all patients respond to these therapies, and current biomarkers are imperfect.

Circulating extracellular vesicles (EVs) are nanovesicles derived from tumor and immune cells, carrying proteins, nucleic acids, and lipids. They represent an accessible and stable source of immunological biomarkers, allowing monitoring of the tumor microenvironment without additional invasive procedures.

This prospective multicenter study aims to:

• Collect and analyze immunological biomarkers present in EVs at baseline and during follow-up.
• Assess their association with objective response to anti-PD-1/PD-L1 treatment, measured according to RECIST 1.1.
• Develop an exploratory composite score combining multiple markers to predict response, stratified by cancer type (NSCLC vs melanoma).
• Prospectively collect biological samples for future exploratory analyses.

Study procedures for participants include:

• Blood sample collection: Four study-specific blood draws performed during standard treatment or tumor assessment visits (baseline, 2nd administration, first evaluation, second evaluation).
• Collection of additional information: Standard immunohistochemistry results for PD-1, PD-L1, CTLA-4, Tim-3, LAG-3, and Tigit; thoraco-abdomino-pelvic CT scans; circulating or tumor DNA genotyping analyses.
• Clinical follow-up: Conducted according to routine care standards, with no changes to treatment or additional study-specific visits.

• Non-Small Cell Lung Cancer
• Melanoma (Skin Cancer)

Ages Eligible for Study

Adult (18-64)Older Adult (65+)

Sexes Eligible for Study

All

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria:

• Age ≥18 years.
• Histologically confirmed diagnosis of non-small cell lung cancer (NSCLC) or locally advanced/metastatic unresectable melanoma.
• Patient scheduled to initiate anti-PD-(L)1 therapy, either as monotherapy or in combination (other immune checkpoint inhibitors, chemotherapy, etc.).
• Baseline tumor assessment performed within 28 days prior to enrollment (CT scan of thorax, abdomen, and pelvis) with at least one measurable lesion according to RECIST 1.1 criteria.
• Life expectancy >6 months.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at enrollment.
• Patient able to provide informed consent and comply with study procedures.
• Patient covered by a social security system or equivalent.

Exclusion Criteria:

• Prior treatment with immunotherapy.
• Presence of EGFR or ALK mutation (applicable only to the lung cohort).
• Presence of another synchronous malignancy.
• Diagnosis of uveal melanoma.
• Treatment with systemic immunosuppressants, including within 28 days prior to enrollment, or corticosteroids >10 mg/day, including within 14 days prior to enrollment.
• Disease not measurable according to RECIST 1.1 criteria.
• Positive serology for HIV, HBV, or HCV.
• Pregnant or breastfeeding women.
• Inability to comply with study follow-up and visits for geographic, social, or psychological reasons.
• Individuals deprived of liberty or under legal guardianship (including curatorship).

Observational Model

Cohort

Time Perspective

Prospective

Lead Sponsor

Centre Georges Francois LeclercOTHER

CGKaderbhai@cgfl.fr03 80 73 75 28

ayoube.zouak@chu-dijon.fr03 80 29 58 64