An observational study in Lung Diseases, Interstitial, NSCLC and Immunotherapy, sponsored by Universitaire Ziekenhuizen KU Leuven. Recruiting at 1 site in Belgium. Open to participants aged 18 Years to 120 Years. Per ClinicalTrials.gov, last updated 2024-07-01.
Sponsored by Universitaire Ziekenhuizen KU Leuven · Observational
The main goal of this prospective non-interventional exploratory study is to characterize the tumor micro-environment of advanced NSCLC in single-cell resolution, prior to immune checkpoint blockade exposure, and correlate the findings to clinical outcome. This approach will allow to generate new hypotheses regarding mechanism of action of ICI and (primary) resistance mechanisms. The long-term goal is that these novel mechanistic insights will be translated to a clinical setting to develop better biomarkers of ICI efficacy. Importantly, since the investigators will also sequentially profile the immune composition of peripheral blood, this research offers an opportunity to develop circulating (non-invasive) biomarkers.
A second aim is to characterize the immune cell composition of bronchoalveolar lavage (BAL) fluid from these ICI-treated cancer patients if they would develop ICI-pneumonitis. These mechanistic insights can directly lead to putative diagnostic biomarkers and therpeutic targets. Since single-cell profiling of blood samples will also be performed, circulating biomarkers of ICI toxicity can also be identified, making non-invasive diagnosis feasible.
The investigators will collect tumor biopsies from 70 st.IV NSCLC patients before start of treatment with immune checkpoint inhibitors. These biopsies are taken during a medically required routine procedure for diagnostic purposes, and will be subjected to the following experimental procedures:
First, scRNA-seq and TCR-seq will be applied on up to 5,000 randomly dissociated cells. Additionally, cell surface protein expression can be integrated with the transcriptional information. Various bioinformatics pipelines, including Seurat, will be used to identify different cell clusters, which through marker gene expression will be assigned to known cell types, cellular subtypes or phenotypes. For instance, this will enable the researchers to monitor the abundance of PD-1/PD-L1 expressing T cells, cytotoxic T-cells, immune-suppressive myeloid cells, etc. The following parameters at single-cell level will be relevant (non-exhaustive):
Blood samples will be subjected to similar experimental procedures. First, PBMC are isolated using Ficoll density gradient centrifugation. Single-cell transcriptome analysis in combination with CITE- seq will be performed on 5000 PBMC. Cellular composition will be determined using the same bioinformatic pipelines as used for processing the tumor biopsies.
As a second objective, immune profiling of the cellular composition of ICI-pneumonitis BAL fluid and PBMC will be performed using scRNA-seq, scTCR-seq and CITE-seq as previously outlined.
3,303 studies on the registry are indexed under Lung Diseases; 355 are open to participants now.
This study's planned enrollment of 70 is below the median of 157 across 929 observational studies indexed under Lung Diseases.
Browse Lung Diseases studies →Universitaire Ziekenhuizen KU Leuven is the lead sponsor of 928 studies on the registry; 261 are open to participants now.
Of its 5 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.
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Patients treated with first-line anti-PD-1 Pembrolizumab (+- chemotherapy) for stage IV non-small cell lung cancer
Exclusion criteria:
Anti-PD-1 monotherapy
Drug: Immune checkpoint inhibitor
Combination anti-PD-1 + chemotherapy
Drug: Chemotherapy + Immune checkpoint inhibitor
Standard-of-care treatment for st.IV NSCLC (no driver mutation, PD-L1 \> 50%)
Also known as: Pembrolizumab
Standard-of-care treatment for st.IV NSCLC (no driver mutation, PD-L1 \< 50%)
Also known as: Pembrolizumab
Immune cell proportions, as determined by scRNA-seq, present in tumor samples of ICI-treated st.IV NSCLC patients attaining objective response or not attaining objective response
By identifying and statistically comparing the percentages of immune cell subtypes present in responding vs. non-responding patients' tumors before start of ICI therapy, we aim to i) understand which immune processes drive response or resistance to ICI ii) identify putative molecular biomarkers iii) identify putative therapeutic targets
Time frame: From date of inclusion until study completion, on average 2 years.
Immune cell proportions, as determined by scRNA-seq, present in peripheral blood of ICI-treated st.IV NSCLC patients attaining objective response or not attaining objective response, before and after 1 cycle of ICI
By identifying and statistically comparing the percentages of immune cell subtypes present in responding vs. non-responding patients' peripheral blood, we aim to i) understand which immune processes drive response or resistance to ICI ii) identify putative molecular biomarkers iii) identify putative therapeutic targets
Time frame: From date of inclusion until study completion, on average 2 years.
Immune cell proportions, as determined by scRNA-seq, present in ICI-induced pneumonitis BAL fluid
By identifying and statistically comparing the percentages of immune cell subtypes present in ICI-/RT-/TKI-induced pneumonitis BAL fluid, we aim to i) understand which immune processes drive these adverse events ii) identify putative molecular biomarkers iii) identify putative therapeutic targets
Time frame: From date of inclusion until study completion, on average 2 years.
Immune cell proportions, as determined by scRNA-seq, present in ICI-induced pneumonitis peripheral blood mononuclear cells
By identifying and statistically comparing the percentages of immune cell subtypes present in ICI-/RT-/TKI-induced pneumonitis peripheral blood mononuclear cells, we aim to i) understand which immune processes drive these adverse events ii) identify putative molecular biomarkers iii) identify putative therapeutic targets
Time frame: From date of inclusion until study completion, on average 2 years.
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Universitaire Ziekenhuizen KU Leuven