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

Trial Summary

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. ^{1 2 3 4 5}

Is 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. ^{1 6 7 8 9}

How 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. ^{1 2 4 5 10}

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.

Eligibility 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.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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 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]

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 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]

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]

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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

PD-L1 expression in circulating tumor cells of advanced non-small cell lung cancer patients treated with nivolumab. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Integrating Circulating Biomarkers in the Immune Checkpoint Inhibitor Treatment in Lung Cancer. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Cellular Expression of PD-L1 in the Peripheral Blood of Lung Cancer Patients is Associated with Worse Survival. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Evaluation of PD-L1 expression on vortex-isolated circulating tumor cells in metastatic lung cancer. [2020]

5. China 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]. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Programmed death-ligand 1 testing of lung cancer cytology specimens obtained with bronchoscopy. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Robust Preanalytical Performance of Soluble PD-1, PD-L1 and PD-L2 Assessed by Sensitive ELISAs in Blood. [2022]

8. Germany 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. [2023]

9. United States 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? [2022]

10. England 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. [2019]