A Single-cell Approach to Identify Biomarkers of Efficacy and Toxicity for ICI in NSCLC
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18-120
SponsorUniversitaire Ziekenhuizen KU Leuven
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Adult M/F/X (>= 18 years)
Histologically and clinically confirmed diagnosis of non-small cell lung cancer (according to IASLC Staging Handbook in Thoracic Oncology v7)
Patients receiving first-line treatment per guidelines
Not included in other clinical trials
Disqualifiers
None
Trial population
Patients treated with first-line anti-PD-1 Pembrolizumab (+- chemotherapy) for stage IV non-small cell lung cancer
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Immune checkpoint inhibitor
DrugStandard-of-care treatment for st.IV NSCLC (no driver mutation, PD-L1 \> 50%)
Chemotherapy + Immune checkpoint inhibitor
DrugStandard-of-care treatment for st.IV NSCLC (no driver mutation, PD-L1 \< 50%)
Treatment groups
70 Participants
are divided into 2 treatment groupsGroup A: NSCLC st.IV (PD-L1 > 50%)1 intervention
Group B: NSCLC st.IV (PD-L1 < 50%)1 intervention
Trial outcomes
Primary outcomes
1
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.2
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.Secondary outcomes
1
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.2
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.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Universitaire Ziekenhuizen KU Leuven
Lead sponsor
KU Leuven
Collaborator
Source ClinicalTrials.gov