PDL-1 Expression on Circulating Tumor Cells in Non-small Cell Lung Cancer (IMMUNO-PREDICT)

Feasibility Study of PD-L1 Expression Analysis on Circulating Tumor Cells by Immunocytochemistry and MDSCs Level Evolution Analysis in Non-small Cell Lung Cancer Treated With PD-L1 or PD1 Inhibitor

Immunotherapy is probably, since the development of therapies targeting EGFR mutations or ALK rearrangement, the most attractive therapeutic perspective in the management of metastatic lung cancer. Among the compounds tested, the inhibitors of the immune checkpoint PROGRAMME DEATH 1 / PROGRAMME DEATH LIGAND 1 (PD-1/PD-L1) have been tested in numerous clinical trials with recently published positive results leading to the approval of one drug in the USA and an expanded access program for two drugs in France. PROGRAMME DEATH LIGAND 1 (PD-L1) expression by tumor cells is strongly associated with the response to such molecules so that the participation in various clinical trials is currently reserved for patients expressing this biomarker and therefore justifies a new invasive biopsy (bronchoscopic or CT-guided) representing a considerable drag on the access to these treatments. Circulating tumor cells (CTCs) isolated by Isolation by Size of Tumor Cells (ISET) offer a direct and non-invasive access to the tumor. It has already been demonstrated that molecular characterization (EGFR, ALK) on these blood samples is possible. We propose to demonstrate the feasibility of the analysis PDL-1 expression in these cells by immunocytochemistry.

Myeloid-Derived Suppressor Cells (MDSCs) are immature myeloid cells that inhibit T cell functions and thus promote tumor growth. These cells frequently express PD-L1. We propose to test whether MDSCs level and its evolution during treatment with PD1 inhibitor is correlated to the response to these drugs.

The main objective of this study is to demonstrate the feasibility of the analysis of PD-L1 expression on CTC

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Biological: blood sample collection for CTC and MDSC analysis

• Study Type: Observational
• Enrollment (Actual): 216

Contacts and Locations

Study Locations

• France
  • Toulouse, France, 31059
    • Larrey hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Stage IV non small lung cancer patients

Description

Inclusion Criteria:

• Stage IV non-small cell lung cancer patient prior to start immunotherapy treatment
• Patients with World Health Organization (WHO) performance status 0-3
• Patients who were informed and had non opposition form signed by investigator
• Patients with healthcare insurance system affiliation

Exclusion Criteria:

• Prior malignancy within 5 years of study entry
• Refusal to participate
• Patient under legal protection

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Stage IV non-small cell lung cancer; Intervention to be done are : - Blood sample collection for CTC and MDSC analysis

Biological: blood sample collection for CTC and MDSC analysis; Isolation of circulating tumor cells from 2 tubes by ISET filtration module. Peripheral blood samples will be collected for CTC analysis within 7 days before commencing treatment (defined as baseline) and following four cycles of immunotherapy,; Analysis of PD-L1 and PD-L2 expression by immunocytochemistry on CTC; Analysis of the expression of PD-L1, PD-L2 , CTLA4 on the histological specimen by immunohistochemistry

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of analysis of PDL-1 expression on circulating tumor cells as assessed by immunocytochemistry analysis	Prior to immunotherapy, after four cycle of immunotherapy	Through the end of study (12 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of CTC expressing PD-L1 after four cycle of immunotherapy as assessed by immunocytochemistry analysis	Prior to immunotherapy, after four cycle of immunotherapy	Through the end of study (12 months)
Evolution of MDSCs count in response to treatment as assessed by MDSCs analysis	Prior to immunotherapy, after four cycle of immunotherapy	Through the end of study (12 months)

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Nicolas GUIBERT, PH, University Hospital of Toulouse

Publications and helpful links

General Publications

• Guibert N, Jones G, Beeler JF, Plagnol V, Morris C, Mourlanette J, Delaunay M, Keller L, Rouquette I, Favre G, Pradines A, Mazieres J. Targeted sequencing of plasma cell-free DNA to predict response to PD1 inhibitors in advanced non-small cell lung cancer. Lung Cancer. 2019 Nov;137:1-6. doi: 10.1016/j.lungcan.2019.09.005. Epub 2019 Sep 6.
• Guibert N, Pradines A, Favre G, Mazieres J. [Finding mutations of interest in circulating tumor DNA helps predict immunotherapy response in lung cancer]. Med Sci (Paris). 2020 May;36(5):437-439. doi: 10.1051/medsci/2020068. Epub 2020 May 26. No abstract available. French.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): October 1, 2021
• Study Completion (Actual): December 1, 2021

Study Registration Dates

• First Submitted: July 6, 2016
• First Submitted That Met QC Criteria: July 6, 2016
• First Posted (Estimated): July 11, 2016

Study Record Updates

• Last Update Posted (Actual): August 29, 2023
• Last Update Submitted That Met QC Criteria: August 25, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: lung cancer; Immunotherapy; circulating tumor cells; Immune checkpoints; immunocytochemistry; MDSC; PD-1/PD-L1; Stage IV non-small cell lung cancer; ISET
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplastic Processes; Neoplasm Metastasis; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Neoplastic Cells, Circulating
• Other Study ID Numbers: 15 7737 02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No