Clinical trial NCT02827344: PDL-1 Expression on Circulating Tumor Cells in Non-small Cell Lung Cancer
Official title: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Lung Cancer
Keywords: PD-1/PD-L1
Immune checkpoints
Immunotherapy
lung cancer
circulating tumor cells
immunocytochemistry
ISET
MDSC
Stage IV non-small cell lung cancer
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2016-07-11
Enrollment: 216
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Stage IV non small lung cancer patients

Brief summary: 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


Eligibility criteria: 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

Primary outcomes:
measure: Feasibility of analysis of PDL-1 expression on circulating tumor cells as assessed by immunocytochemistry analysis
timeFrame: Through the end of study (12 months)
Secondary outcomes:
measure: Percentage of CTC expressing PD-L1 after four cycle of immunotherapy as assessed by immunocytochemistry analysis
timeFrame: Through the end of study (12 months)
measure: Evolution of MDSCs count in response to treatment as assessed by MDSCs analysis
timeFrame: Through the end of study (12 months)
Other outcomes:
Locations:
city: Toulouse
country: France
facility: Larrey Hospital
Study officials:
affiliation: University Hospital of Toulouse
name: Nicolas GUIBERT, PH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.