Validation of the TheraSure CNI Monitor Under Immune Checkpoint Therapy (Hereinafter: Immunotherapy) in NSCLC in Palliative Therapy

Study Overview
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Brief Summary
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This is a prospective, non-interventional, national study planned at three centers in patients with non-curative NSCLC receiving immunotherapy. At present, PD-L1 expression or tumor mutation burden serve as surrogate parameters for response to immunotherapy. However, the problem for clinicians is that not all patients with positive findings respond to this form of therapy. Cell-free DNA (cf-DNA) can be detected in blood plasma. Tumor cells almost always have chromosomal instabilities (or copy-number variations (CNV)), which can be detected using next-generation sequencing (NGS), also in the cf-DNA. These CNV can be quantified and given as a cf-DNA copy number instability score (CNI value). TheraSure CNI Monitor is a highly sensitive method that can detect as little as 0.5% tumor DNA in plasma. In preliminary work in a cohort of 56 patients with various types of cancer (including: breast, colon, lung, ovary, melanoma) in advanced stages, the TheraSure CNI monitor was already evaluated in the monitoring of immunotherapy. In 51 of the 56 patients, increased CKD values were measured before the start of therapy compared to a normal group of 126 individuals. To predict the success of the therapy, further blood samples were used after the first and second therapy cycle and threshold values were set for the minimal expected decrease in the CKD value in the event of therapy response. A therapy failure could be predicted with a high positive predictive value, cases of hyperprogression could be detected earlier than by routine imaging. In addition, pseudoprogression could be distinguished from true progression using the CRF value. The CNI monitor on cell-free DNA is to be used prospectively in 170 patients. The primary objective of the study is the prediction of primary progression under immunomonotherapy (defined as PD within 6 months after RECIST) with a predictive value for progression (PPV) of ≥50%.

Official Title
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Validation of the TheraSure CNI Monitor Under Immune Checkpoint Therapy (Hereinafter: Immunotherapy) in NSCLC in Palliative Therapy

Conditions
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NSCLC

Intervention / Treatment
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* Other: No Intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent form Patients with NSCLC, non-curatively treatable stage III and stage IV in palliative treatment situation with immunotherapy (in the sense of monotherapy, double immunotherapy or combination with chemotherapy) Exclusion Criteria: Persons unable to understand the nature, importance and scope of the clinical trial Participation in an interventional study Age <18 years Hb value <9g/dl

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: No Intervention|No Intervention|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PD | The TheraSure CKD monitor predicts primary progression on immunomonotherapy (defined as PD within 6 months of RECIST) with a predictive value for progression (PPV) of ≥50%. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | The TheraSure CRF monitor predicts progression-free survival (PFS) in cancer patients receiving immunotherapy. The aim is to determine a significantly different (p<.05) hazard ratio with a describable dichotomized result of the cell-free tumor DNA. | 6 months | 
| OS | The TheraSure CRI Monitor predicts overall survival (OS) in cancer patients receiving immunotherapy. The aim is to determine a significantly different (p<.05) hazard ratio with a describable dichotomized result of the cell-free tumor DNA. | 6 months |