Clinical trial NCT04791215: Circulating Tumor DNA Alterations in Non-small Cell Lung Cancer Patients Treated With Pembrolizumab
Official title: An Observational Study of Circulating Tumor DNA Genetic Alterations in Non-small Cell Lung Cancer Patients Treated With Pembrolizumab
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Non Small Cell Lung Cancer
Keywords: Cancer
Immune system
Lung Cancer
Pembrolizumab
Lead sponsor: Columbia University
Sponsor class: OTHER
First posted: 2021-03-10
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All male and females with a diagnosis of NSCLC with a protein that acts as a kind of "brake" to keep the body's immune responses under control PD-L1 TPS ≥1% and no known alterations in driver genes epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or Proto-oncogene tyrosine-protein kinase (ROS1).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Radiologic response to immune checkpoint blockade (ICB) by clonal dynamics of serial ctDNA in 1st line NSCLC patients receiving pembrolizumab monotherapy.
timeFrame: 5 years
Secondary outcomes:
measure: To characterize kinetic profiles of tumor mutations and see if they are predictive of overall survival (OS) and progression-free survival (PFS).
timeFrame: 5 years
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Brian Henick, MD
role: PRINCIPAL_INVESTIGATOR
References: