Liquid Biopsy Testing for Lung Cancer
Recruiting in Palo Alto (17 mi)
Age: Any Age
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Ballad Health
Must be taking:Anti-PD-1/L1
Disqualifiers: Radiation therapy, Small-cell lung cancer
No Placebo Group
Trial Summary
What is the purpose of this trial?This is a prospective pilot study to assess dynamic changes of plasma cell-free RNA (cfRNA) PD-L1 expression in patients with lung cancer undergoing immune checkpoint inhibitor (ICI) based therapy. Results will be correlated with radiographic assessment of immunotherapy treatment response and plasma NGS ctDNA.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop your current medications. It focuses on patients already receiving certain immune therapies, so you might be able to continue those treatments.
What data supports the effectiveness of the treatment Plasma PD-L1 Testing for lung cancer?
Research shows that PD-L1 expression in circulating tumor cells can help identify lung cancer patients who might respond to immunotherapy, offering a non-invasive way to guide treatment decisions.
12345Is liquid biopsy testing for lung cancer safe for humans?
The research does not provide specific safety data for liquid biopsy testing in humans, but it does mention that PD-L1 testing, which is part of the liquid biopsy process, is commonly used in lung cancer care, suggesting it is generally considered safe.
16789How does liquid biopsy testing for lung cancer differ from other treatments?
Liquid biopsy testing for lung cancer is unique because it uses a blood test to analyze circulating tumor cells for PD-L1 expression, which can help determine the best treatment options. This method is less invasive than traditional tissue biopsies and can provide a more comprehensive view of the tumor's characteristics, potentially leading to more personalized and effective treatment plans.
124510Eligibility Criteria
This trial is for individuals with lung cancer, specifically non-small cell lung cancer, who are undergoing treatment with immune checkpoint inhibitors. Participants will have their blood tested to monitor changes in a specific RNA linked to the body's response to therapy.Inclusion Criteria
I have advanced lung cancer and am receiving immunotherapy without planned radiation.
Exclusion Criteria
My lung cancer is of the small-cell type.
I have not received any anti-PD-1/L1 treatments.
I am scheduled for my first radiation therapy.
Participant Groups
The study is testing a new way of monitoring lung cancer treatment using 'liquid biopsy' blood tests. These tests measure PD-L1 levels in RNA from plasma and compare them with imaging results and DNA markers from circulating tumor cells.
1Treatment groups
Experimental Treatment
Group I: plasma NGS ctDNA and plasma cfRNA PD-L1 expressionExperimental Treatment1 Intervention
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Ballad Health Cancer CareKingsport, TN
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Who is running the clinical trial?
Ballad HealthLead Sponsor
References
PD-L1 expression in circulating tumor cells of advanced non-small cell lung cancer patients treated with nivolumab. [2019]Inhibitors of the PD-1/PD-L1 immune checkpoint have become a standard of care in non-small cell lung cancer (NSCLC). Patient selection, currently based on PD-L1 expression on tumor tissue, is limited by its temporal and spatial heterogeneity. We hypothesized that liquid biopsy with PD-L1 analysis on circulating tumor cells (CTCs) might overcome this limitation.
Integrating Circulating Biomarkers in the Immune Checkpoint Inhibitor Treatment in Lung Cancer. [2020]Immune checkpoint inhibitors are now a cornerstone of treatment for non-small cell lung cancer (NSCLC). Tissue-based assays, such as Programmed cell death protein 1 (PD-L1) expression or mismatch repair deficiency/microsatellite instability (MMRD/MSI) status, are approved as treatment drivers in various settings, and represent the main field of research in biomarkers for immunotherapy. Nonetheless, responses have been observed in patients with negative PD-L1 or low tumor mutational burden. Some aspects of biomarker use remain poorly understood and sub-optimal, in particular tumoral heterogeneity, time-evolving sampling, and the ability to detect patients who are unlikely to respond. Moreover, tumor biopsies offer little insight into the host's immune status. Circulating biomarkers offer an alternative non-invasive solution to address these pitfalls. Here, we summarize current knowledge on circulating biomarkers while using liquid biopsies in patients with lung cancer who receive treatment with immune checkpoint inhibitors, in terms of their potential as being predictive of outcome as well as their role in monitoring ongoing treatment. We address host biomarkers, notably circulating immune cells and soluble systemic immune and inflammatory markers, and also review tumor markers, including blood-based tumor mutational burden, circulating tumor cells, and circulating tumor DNA. Technical requirements are discussed along with the current limitations that are associated with these promising biomarkers.
Cellular Expression of PD-L1 in the Peripheral Blood of Lung Cancer Patients is Associated with Worse Survival. [2019]Background: Lung cancer treatment has become increasingly dependent upon invasive biopsies to profile tumors for personalized therapy. Recently, tumor expression of programmed death-ligand 1 (PD-L1) has gained interest as a potential predictor of response to immunotherapy. Circulating biomarkers present an opportunity for tumor profiling without the risks of invasive procedures. We characterized PD-L1 expression within populations of nucleated cells in the peripheral blood of lung cancer patients in hopes of expanding the role of liquid biopsy in this setting.Methods: Peripheral blood samples from a multi-institutional prospective study of patients with clinical diagnosis of lung cancer were subjected to cytomorphometric and immunohistochemical evaluation using single-cell, automated slide-based, digital pathology. PD-L1 expression was determined by immunofluorescence.Results: PD-L1 expression was detected within peripheral circulating cells associated with malignancy (CCAM) in 26 of 112 (23%) non-small cell lung cancer patients. Two distinct populations of nucleated, nonhematolymphoid, PD-L1-expressing cells were identified; cytokeratin positive (CK+, PD-L1+, CD45-) and cytokeratin negative (CK-, PD-L1+, CD45-) cells, both with cytomorphometric features (size, nuclear-to-cytoplasm ratio) consistent with tumor cells. Patients with >1.1 PD-L1(+) cell/mL (n = 14/112) experienced worse overall survival than patients with ≤1.1 PD-L1(+) cell/mL (2-year OS: 31.2% vs. 78.8%, P = 0.00159). In a Cox model adjusting for stage, high PD-L1(+) cell burden remained a significant predictor of mortality (HR = 3.85; 95% confidence interval, 1.64-9.09; P = 0.002).Conclusions: PD-L1 expression is detectable in two distinct cell populations in the peripheral blood of lung cancer patients and is associated with worse survival.Impact: These findings could represent a step forward in the development of minimally invasive liquid biopsies for the profiling of tumors. Cancer Epidemiol Biomarkers Prev; 26(7); 1139-45. ©2017 AACR.
Evaluation of PD-L1 expression on vortex-isolated circulating tumor cells in metastatic lung cancer. [2020]Metastatic non-small cell lung cancer (NSCLC) is a highly fatal and immunogenic malignancy. Although the immune system is known to recognize these tumor cells, one mechanism by which NSCLC can evade the immune system is via overexpression of programmed cell death ligand 1 (PD-L1). Recent clinical trials of PD-1 and PD-L1 inhibitors have returned promising clinical responses. Important for personalizing therapy, patients with higher intensity staining for PD-L1 on tumor biopsies responded better. Thus, there has been interest in using PD-L1 tumor expression as a criterion for patient selection. Currently available methods of screening involve invasive tumor biopsy, followed by histological grading of PD-L1 levels. Biopsies have a high risk of complications, and only allow sampling from limited tumor sections, which may not reflect overall tumor heterogeneity. Circulating tumor cell (CTC) PD-L1 levels could aid in screening patients, and could supplement tissue PD-L1 biopsy results by testing PD-L1 expression from disseminated tumor sites. Towards establishing CTCs as a screening tool, we developed a protocol to isolate CTCs at high purity and immunostain for PD-L1. Monitoring of PD-L1 expression on CTCs could be an additional biomarker for precision medicine that may help in determining response to immunotherapies.
[Distribution and Clinical Significance of CTLA-4, PD-1 and PD-L1 in Peripheral Blood of Patients with Small Cell Lung Cancer]. [2018]The aim of this study is to explore cytotoxic T lymphocyte associated antigen 4 (CTLA-4), programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) distribution and clinical value in liquid biopsy (such as blood) of small cell lung cancer (SCLC) patients.
Programmed death-ligand 1 testing of lung cancer cytology specimens obtained with bronchoscopy. [2019]Programmed death-ligand 1 (PD-L1) expression testing is recommended by guidelines for patients with advanced non-small cell lung cancer (NSCLC). The primary objective of the current study was to determine the success rate of PD-L1 testing from cytology cell block samples obtained by bronchoscopic needle aspiration. The secondary objective was the assessment of the difference in specimen adequacy acquired via needles of different gauges.
Robust Preanalytical Performance of Soluble PD-1, PD-L1 and PD-L2 Assessed by Sensitive ELISAs in Blood. [2022]The interaction between programmed death-1 receptor PD-1 and its ligands PD-L1 and PD-L2 is involved in self-tolerance, immune escape of cancer, cardiovascular diseases, and COVID-19. As blood-based protein markers they bear great potential to improve oncoimmunology research and monitoring of anti-cancer immunotherapy. A variety of preanalytical conditions were tested to assure high quality plasma sample measurements: (i) different time intervals and storage temperatures before and after blood centrifugation; (ii) fresh samples and repeated freeze-thaw-cycles; (iii) different conditions of sample preparation before measurement. Concerning short-term stability, acceptable recoveries for PD-1 between 80 and 120% were obtained when samples were kept up to 24 h at 4 and 25 °C before and after blood centrifugation. Similarly, recoveries for PD-L2 were acceptable for 24 h at 4 °C and 6 h at 25 °C before blood centrifugation and up to 24 h at 4 and 25 °C after centrifugation. Variations for PD-L1 were somewhat higher, however, at very low signal levels. Sample concentrations (ng/mL) were neither affected by the freezing process nor by repeated freeze-thaw cycles with coefficients of variation for PD-1: 9.1%, PD-L1 6.8%, and PD-L2 4.8%. All three biomarkers showed good stability regarding preanalytic conditions of sample handling enabling reliable and reproducible quantification in oncoimmunology research and clinical settings of anti-cancer immunotherapy.
Correlation of PD-L1 expression on tumour cells between diagnostic biopsies and surgical specimens of lung cancer in real life with respect to biopsy techniques and neoadjuvant treatment. [2023]Programmed death-ligand 1 (PD-L1) testing is performed mainly on biopsy specimens in patients with advanced lung cancer. It is questionable whether the small amount of tissue analysed in biopsies may represent the true PD-L1 expression of a tumour.
PD-L1 testing using the clone 22C3 pharmDx kit for selection of patients with non-small cell lung cancer to receive immune checkpoint inhibitor therapy: are cytology cell blocks a viable option? [2022]Programmed death ligand 1 (PD-L1) testing of non-small cell lung cancer (NSCLC) specimens helps select patients most likely to respond to immune checkpoint inhibitors. PD-L1 immunohistochemical testing is approved for formalin-fixed, paraffin-embedded (FFPE) surgical pathology specimens; however, the testing performance on FFPE cytology cell block specimens is unknown.
Comparison of PD-L1 immunohistochemistry assays and response to PD-1/L1 inhibitors in advanced non-small-cell lung cancer in clinical practice. [2019]Several studies have demonstrated analytical comparability between different PD-L1 assays, but their clinical validity in non-small-cell lung cancer in terms of response to treatment outside clinical trials has not been established. The aim of our study is to assess the analytical performance of laboratory-developed tests for Ventana SP263 and Agilent/Dako 22C3, and to investigate the association between PD-L1 assays and response to PD-1/L1 inhibitors.