Liquid Biopsy Testing for Lung Cancer

Overseen By Charles Mays, PhD, CCRP, CCRC

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Ballad Health

Must be taking: Anti-PD-1/L1

Disqualifiers: Radiation therapy, Small-cell lung cancer

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to study how a liquid biopsy test, which examines cell-free RNA in the blood, can track changes during lung cancer treatment. It focuses on patients with advanced non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitor therapy. Researchers will compare results with traditional imaging to evaluate treatment response. Suitable candidates include those with stage IV or inoperable stage IIIB NSCLC who are not planned for primary radiation therapy and are receiving specific immune-based treatments, such as Plasma PD-L1 Testing.

As an unphased trial, this study allows patients to contribute to innovative research that could improve future lung cancer treatments.

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 prior data suggests that plasma PD-L1 testing is safe?

Research has shown that plasma PD-L1 testing is generally easy for patients to handle. In one study with 22 patients who had advanced lung cancer, 90.9% completed the test using samples from a procedure called cytology. This indicates the process usually works well without causing problems for patients.

Other studies have indicated that checking PD-L1 levels in plasma can help predict how well patients will respond to certain cancer treatments. These findings suggest that the test is helpful and does not cause major side effects. Overall, evidence suggests that plasma PD-L1 testing is safe for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about plasma PD-L1 testing for lung cancer because it offers a non-invasive way to assess tumor characteristics using a blood sample, also known as a liquid biopsy. Unlike traditional biopsies that require tissue samples through surgery or needle procedures, this method analyzes circulating tumor DNA (ctDNA) and cell-free RNA (cfRNA) from the blood, making it safer and more convenient for patients. Additionally, it provides real-time insights into tumor changes, potentially allowing for more personalized and timely adjustments in treatment plans. This approach could lead to faster and more accurate treatment decisions compared to conventional methods.

What evidence suggests that plasma PD-L1 testing is effective for lung cancer?

This trial will evaluate plasma PD-L1 testing as a method for predicting treatment responses in lung cancer patients. Research has shown that testing for PD-L1 in blood plasma might help predict how well lung cancer patients respond to certain treatments. Studies have found that patients with positive PD-L1 results in their blood have similar survival rates to those with positive results from tissue tests, living about 15 months on average. Additionally, the presence of PD-L1 in the blood often links to a higher number of mutations in the tumor, which can indicate a better response to immunotherapy. Blood tests for PD-L1 might help identify patients who could benefit more from PD-L1 inhibitors. Overall, these findings suggest that plasma PD-L1 testing could be a useful tool in guiding lung cancer treatment. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

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.

I understand and agree to participate in the study voluntarily.

I am currently on a treatment that includes an anti-PD-1/L1 drug.

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive immune checkpoint inhibitor (ICI) based therapy and undergo plasma cfRNA PD-L1 testing

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Plasma PD-L1 Testing

Trial Overview 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.

How Is the Trial Designed?

Group I: plasma NGS ctDNA and plasma cfRNA PD-L1 expression Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Ballad Health

Lead Sponsor

Trials

4

Recruited

1,300+

Published Research Related to This Trial

In a study of 22 patients with advanced non-small cell lung cancer (NSCLC), 90.9% successfully underwent PD-L1 testing using cytology samples obtained through bronchoscopic needle aspiration, indicating high efficacy of this method for testing.

The study found no significant differences in PD-L1 testing success rates based on the type of needle used or its size, suggesting that various needle techniques can be effectively employed without compromising test adequacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed death-ligand 1 testing of lung cancer cytology specimens obtained with bronchoscopy. Stoy, SP., Rosen, L., Mueller, J., et al.[2019]

Metastatic non-small cell lung cancer (NSCLC) often evades the immune system through overexpression of PD-L1, but recent trials show that PD-1 and PD-L1 inhibitors can lead to promising responses, especially in patients with higher PD-L1 levels in tumor biopsies.

The study proposes using circulating tumor cell (CTC) PD-L1 levels as a non-invasive screening method to assess PD-L1 expression, which could provide a more comprehensive view of tumor heterogeneity and help personalize immunotherapy treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of PD-L1 expression on vortex-isolated circulating tumor cells in metastatic lung cancer. Dhar, M., Wong, J., Che, J., et al.[2020]

The study analyzed 302 non-small-cell lung cancer samples using two PD-L1 assays (Ventana SP263 and Agilent/Dako 22C3) and found a high level of agreement between the assays, with a concordance correlation coefficient of 0.86, indicating they can be reliably used interchangeably.

The SP263 assay's 10% cut-off was significantly associated with treatment response to PD-1/L1 inhibitors, while the 22C3 assay showed significant associations at all tested cut-offs (1%, 5%, and 10%), suggesting that both assays can effectively predict patient responses to these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of PD-L1 immunohistochemistry assays and response to PD-1/L1 inhibitors in advanced non-small-cell lung cancer in clinical practice. Villaruz, LC., Ancevski Hunter, K., Kurland, BF., et al.[2019]

In a study of 112 non-small cell lung cancer patients, PD-L1 expression was found in circulating tumor-associated cells in 23% of cases, indicating a potential for using liquid biopsies to profile tumors non-invasively.

Patients with a higher burden of PD-L1(+) cells in their blood (>1.1 cells/mL) had significantly worse overall survival rates (31.2% at 2 years) compared to those with lower levels (78.8% at 2 years), suggesting that PD-L1 levels could be a critical biomarker for predicting patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cellular Expression of PD-L1 in the Peripheral Blood of Lung Cancer Patients is Associated with Worse Survival. Boffa, DJ., Graf, RP., Salazar, MC., et al.[2019]

The interaction between PD-1 and its ligands PD-L1 and PD-L2 is crucial for understanding immune responses in cancer and other diseases, and reliable measurement of these proteins can enhance cancer immunotherapy research.

The study confirmed that PD-1, PD-L1, and PD-L2 biomarkers remain stable under various preanalytical conditions, allowing for accurate quantification in clinical settings, which is essential for monitoring anti-cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robust Preanalytical Performance of Soluble PD-1, PD-L1 and PD-L2 Assessed by Sensitive ELISAs in Blood. Krueger, K., Mayer, Z., Kottmaier, M., et al.[2022]

In a study of 290 chemotherapy-naive small cell lung cancer (SCLC) patients, CTLA-4 was found to be highly expressed in regulatory T cells, while PD-1 levels decreased in CD8+ T cells, indicating their roles in immune regulation specific to SCLC.

The level of CD4+CD25+CTLA-4+ cells decreased after the second cycle of chemotherapy, suggesting it may have potential as a biomarker for predicting treatment efficacy, although it was not associated with patient survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Distribution and Clinical Significance of CTLA-4, PD-1 and PD-L1 in Peripheral Blood of Patients with Small Cell Lung Cancer]. Li, H., Liu, Y., Liu, Y., et al.[2018]

In a study involving 96 patients with advanced non-small cell lung cancer (NSCLC), liquid biopsy analysis of circulating tumor cells (CTCs) showed that PD-L1 expression was more frequently positive in CTCs (83%) compared to tissue samples (41%), indicating that CTCs may provide a more reliable assessment of PD-L1 status.

High numbers of pre-treatment CTCs were linked to a greater risk of death and disease progression, suggesting that monitoring CTCs could help predict patient outcomes and improve treatment strategies for those receiving PD-1 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1 expression in circulating tumor cells of advanced non-small cell lung cancer patients treated with nivolumab. Guibert, N., Delaunay, M., Lusque, A., et al.[2019]

In a study of 232 advanced stage non-small cell lung cancer (NSCLC) patients, PD-L1 testing on cytology cell block specimens showed similar tumor proportion scores (TPS) compared to surgical pathology specimens, indicating that cytology samples can be reliably used for PD-L1 testing.

Patients with a PD-L1 TPS ≥50% who were treated with pembrolizumab exhibited comparable response and disease control rates regardless of whether their PD-L1 testing was done on cytology or surgical pathology specimens, suggesting effective treatment options can be based on cytology results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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? Torous, VF., Rangachari, D., Gallant, BP., et al.[2022]

Immune checkpoint inhibitors are crucial for treating non-small cell lung cancer (NSCLC), but traditional tissue-based biomarkers like PD-L1 expression may not fully predict patient responses, as some patients with negative PD-L1 still respond to treatment.

Circulating biomarkers from liquid biopsies present a promising non-invasive alternative for predicting treatment outcomes and monitoring therapy, addressing limitations of tissue biopsies by providing insights into both tumor characteristics and the host's immune status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrating Circulating Biomarkers in the Immune Checkpoint Inhibitor Treatment in Lung Cancer. Duchemann, B., Remon, J., Naigeon, M., et al.[2020]

In a study of 113 lung cancer patients, there was a significant correlation in PD-L1 expression between biopsy samples and surgical resection specimens, indicating that biopsy results can reflect tumor characteristics.

However, the moderate concordance rate of 78% when using a cut-off of ≥50% PD-L1 expression suggests that biopsy results should be interpreted cautiously when making treatment decisions, especially in the context of neoadjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Gompelmann, D., Sinn, K., Brugger, J., et al.[2023]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2950195423001303

Plasma cell-free RNA PD-L1 or tissue PD-L1 protein ... OS outcomes were identical in the plasma cfRNA PD-L1 positive and tissue PD-L1 protein positive patient cohorts (median OS 15 months; landmark 3-year OS 30 %; ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06849518

Study of Longitudinal Plasma PD-L1 Testing With ... 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8992448/

Using cfRNA as a tool to evaluate clinical treatment ... Total cfRNA may be useful in predicting clinical outcomes. PD-L1 gene expression may provide a biomarker to predict response to PD-L1 inhibition ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.e15049

Plasma cell free PD-L1 RNA expression correlated with ... Plasma PD-L1 cfRNA expression correlated with a higher association of tissue TMB high findings than tissue PD-L1 positive patients.

5. circulogene.com circulogene.com/wp-content/uploads/2022/11/MKT-0010-Lung-Cancer-Brochure-Rev-2.pdf

Comprehensive Molecular Testing for Lung Cancer Survival Function. 1. Study demonstrates plasma cfRNA. PD-L1 is predictive of immunotherapy benefit in advanced NSCLC (compared to chemotherapy). The ECU study ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06849518

Study of Longitudinal Plasma PD-L1 Testing With ... 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 ...

7. preprints.org preprints.org/manuscript/202208.0208/v1/download

Plasma Cell-free RNA PD-L1 Expression and Overall ... Plasma cfRNA PD-L1 was associated with a statistically significant survival benefit from ICI-based treatment compared to chemotherapy in the ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S155608642102284X

Liquid Biopsy for Advanced NSCLC: A Consensus ... Although those patients with the highest level of PD-L1 expression consistently have the most benefit, essentially all studies also reveal improved survival in ...

9. withpower.com withpower.com/trial/liquid-biopsy-testing-for-lung-cancer-af493

Liquid Biopsy Testing for Lung Cancer In a study of 22 patients with advanced non-small cell lung cancer (NSCLC), 90.9% successfully underwent PD-L1 testing using cytology samples obtained through ...