Circulating Tumor DNA Alterations in Non-small Cell Lung Cancer Patients Treated With Pembrolizumab

Terminated

• Conditions: Non Small Cell Lung Cancer
• Interventions: Other: Observational

• Registration Number: NCT04791215
• Lead Sponsor: Columbia University

Brief Summary

The purpose of this study is to learn how to use blood tests to better predict how patients with non-small cell lung cancer, who are taking pembrolizumab for cancer treatment, will respond to treatment with pembrolizumab, and to understand how the immune system and cancer interact.

Tests will be performed on tumor tissue and blood samples, and imaging assessments will be reviewed in order to monitor how well each patient responds to treatment. This is an observational study, so participants will not receive cancer treatment, other than the treatment received as standard of care.

Detailed Description

The primary and secondary endpoints of this study are to determine the kinetics of Circulating tumor DNA (ctDNA) as defined by a set of patient-specific tumor mutations. The analysis will be undertaken using the Signatera Assay from Natera. Circulating tumor DNA in plasma samples obtained over the course of pembrolizumab treatment will be assessed by high-intensity, next-generation genetic sequencing to identify genomic alterations in genes. The assay will target 16 defined patient specific mutations. Data acquired will be analyzed to characterize the association between these genetic elements, clinical response, and durability of responses. There will be prospective and retrospective groups for the study. Samples will be collected from patients in the prospective cohort who have been treated with pembrolizumab monotherapy at Columbia University Irving Medical Center under standard of care treatment. Subjects in the retrospective cohort will provide genetic data.

Study Timeline

• Study Start: 2020-02-01
• Study First Submitted: 2021-03-08
• Study First Submitted QC: 2021-03-08
• Study First Posted: 2021-03-10
• Primary Completion: 2023-04-12
• Study Completion: 2023-04-12
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-23
• Last Update Posted: 2024-10-26

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

1. Diagnosis of NSCLC with a protein that acts as a kind of "brake" to keep the body's immune responses under control called Programmed Death Ligand-1 (PD-L1) Tumor Proportion Score (TPS) ≥ 1% and no known alterations in driver genes epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or receptor tyrosine kinase (ROS1).
2. Retrospective cohort: subjects must consent to provide genetic data from previous whole exome sequencing (WES) in the form of FASTQ/BAM files (files that represent aligned genetic sequences) for creation of plasma ctDNA panels.
3. Prospective cohort: Subjects must consent to provide available archived tumor and blood for WES (matched tumor and normal) for creation of plasma ctDNA panels. The tumor sample must be from a site that was not previously irradiated or has progressed after radiation.
4. Ability to understand and the willingness to sign a written informed consent document.
5. Willing to comply with clinical trial instructions and requirements.
6. Both men and women of all races and ethnic groups are eligible for this trial

Exclusion Criteria

1. Age <18 years
2. Known history of autoimmune disease or other medical conditions that would preclude safe treatment with pembrolizumab.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Retrospective Sample Collection	Observational	Retrospective sample collection from participants that consent to provide genetic data from previous whole exome sequencing (WES) in the form of files for creation of plasma ctDNA panels.
Prospective Sample Collection	Observational	Prospective sample collection from participants treated with pembrolizumab monotherapy at Columbia University Irving Medical Center under standard of care treatment. Prospective cohort subjects must consent to provide available archived tumor and blood for whole exome sequencing (WES) (matched tumor and normal) for creation of plasma ctDNA panels. The tumor sample must be from a site that was not previously irradiated or has progressed after radiation.

Primary Outcome Measures

Name	Time	Method
Radiologic response to immune checkpoint blockade (ICB) by clonal dynamics of serial ctDNA in 1st line NSCLC patients receiving pembrolizumab monotherapy.	5 years	Radiologic response to immune checkpoint blockade (ICB) by clonal dynamics of serial ctDNA in 1st line NSCLC participants receiving pembrolizumab monotherapy. Imaging studies will be performed per RECIST 1.1. Radiologic response measured as the average time between randomization and detection of overt progression or response by ctDNA compared to RECIST 1.1.

Secondary Outcome Measures

Name	Time	Method
To characterize kinetic profiles of tumor mutations and see if they are predictive of overall survival (OS) and progression-free survival (PFS).	5 years	To characterize kinetic profiles of defined tumor mutations in tumor fraction ctDNA and evaluate whether they are predictive of overall survival (OS) and progression-free survival (PFS). A blood-based ctDNA assay offers the advantage of a read-out of these temporal changes, with the prospect of kinetic assessment of tumor fraction ctDNA being predictive for early response or progression to immunotherapy. The ability to assess temporal changes in tumor genetics will give insight into tumor clonal evolution and immune editing of specific neoantigens, which may enable leveraging of these insights for future diagnostic and therapeutic improvements.

Trial Locations

Locations (1)

Columbia University Irving Medical Center; 🇺🇸 New York, New York, United States