A Single-cell Approach to Identify Biomarkers of Efficacy and Toxicity for ICI in NSCLC

NCT04807114 | Recruiting DMC

• 1 other identifier: S63531
• Study Type: observational
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Lung Diseases, Interstitial; NSCLC; Immunotherapy

Outcome Measures

Primary Outcomes (2)

• 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

  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

  From date of inclusion until study completion, on average 2 years.

Secondary Outcomes (2)

• Immune cell proportions, as determined by scRNA-seq, present in ICI-induced pneumonitis BAL fluid

  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

  From date of inclusion until study completion, on average 2 years.

Study Arms (2)

NSCLC st.IV (PD-L1 > 50%)

Anti-PD-1 monotherapy

Drug: Immune checkpoint inhibitor

NSCLC st.IV (PD-L1 < 50%)

Combination anti-PD-1 + chemotherapy

Drug: Chemotherapy + Immune checkpoint inhibitor

Interventions

Immune checkpoint inhibitor DRUG

Standard-of-care treatment for st.IV NSCLC (no driver mutation, PD-L1 \> 50%)

Also known as: Pembrolizumab

NSCLC st.IV (PD-L1 > 50%)

Chemotherapy + Immune checkpoint inhibitor DRUG

Standard-of-care treatment for st.IV NSCLC (no driver mutation, PD-L1 \< 50%)

Also known as: Pembrolizumab

NSCLC st.IV (PD-L1 < 50%)

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients treated with first-line anti-PD-1 Pembrolizumab (+- chemotherapy) for stage IV non-small cell lung cancer

You may qualify if:

• 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
• Signed informed consent form

You may not qualify if:

• Collected material not suitable for further processing in this study (e.g. bad quality). This decision will be made in consultation with a lab technician and/or bio-informatician, specialized in single-cell analysis.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead
• KU Leuven: collaborator

Study Sites (1)

Universitaire Ziekenhuizen Leuven

Leuven, 3000, Belgium

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

* Tumor and BAL samples will not be retained * PBMC samples will be stored at -80°C, for batch processing

MeSH Terms

Conditions

Lung Diseases, Interstitial

Interventions

Immune Checkpoint Inhibitors; pembrolizumab; Drug Therapy

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Therapeutics

Study Officials

• Els Wauters, MD, PhD

  University Hospitals - KU Leuven

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Els Wauters

CONTACT

+3216340942; els.wauters@uzleuven.be

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2021
• First Posted: March 19, 2021
• Study Start: February 1, 2020
• Primary Completion: January 31, 2025
• Study Completion: January 31, 2025
• Last Updated: July 1, 2024

Record last verified: 2024-06

Locations

BE (1)