Spanish Lung Liquid vs. Invasive Biopsy Program (SLLIP)

Study Overview
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Brief Summary
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Tumor Derived cell free DNA (cfDNA) is increasingly used in the clinic to obtain genotype information about lung cancer, but its concordance with concurrent tumor-derived sequenced data is not known. The primary objective of this study is to demonstrate the non-inferiority of cfDNA-based versus tumor tissue-based genotyping.

Detailed Description
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Primary objective: To demonstrate the non-inferiority of cfDNA-based versus tumor tissue-based genotyping as it pertains to the detection of clinically-actionable biomarkers in first line, treatment naïve, metastatic non-squamous NSCLC. The following secondary objectives will be studied: Turn around Time (TAT) of cfDNA vs. tissue results. Time to treatment (TtT) initiation. Quantity not sufficient rate (QNS) of tissue for clinically-actionable biomarker testing. Tumor Not Detected (TND) rate of cfDNA in blood. Rescue rate of QNS samples using cfDNA-derived genotyping. Rate response for patients that are actionable biomarker positive (either in cDNA or tissue) treated with target-drugs according investigator criteria. Up to three RECIST assessments per patient will be retrospectively done by external personnel (no investigational team). Rate of discovery of genomically mediated, acquired resistance to targeted therapies in the biomarker-positive subsets.

Official Title
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Spanish Lung Liquid vs. Invasive Biopsy Program

Conditions
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Lung Cancer

Intervention / Treatment
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* Diagnostic Test: Guardant360


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients biopsy-proven, metastatic, previously untreated, non-squamous non-small cell lung cancer (NSCLC). Patients may have received adjuvant cytotoxic chemotherapy, but not targeted neo-adjuvant or adjuvant therapy. Age ≥ 18 years Ability to understand a written informed consent document, and the willingness to sign it. Willingness to provide blood sample at the time points defined in Table 1 [pre-treatment, Day 14 (+/- 7 days) and End of Study]. Patient has or will have standard-of-care tissue genotyping ordered. Stable Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 Exclusion Criteria: Pregnancy, recorded from clinical records Any concurrent, non-cutaneous, malignancy (with the exception of early stage non-invasive cervical cancer). Any prior cancer must have occurred more than 5 years prior with no evidence of currently active disease

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 |
| --- |
|Diagnostic Test: Guardant360|Cell-free circulating tumor DNA (cfDNA) targeted next-generation sequencing (NGS) panel.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-inferiority of cell free DNA (cfDNA)-based versus tumor tissue-based genotyping | Demonstrate the non-inferiority of cell free DNA (cfDNA)-based versus tumor tissue-based genotyping as it pertains to the detection of clinically-actionable biomarkers in first line, treatment naïve, metastatic non-squamous Non-small cell lung cancer (NSCLC). | From date of inclusion until 12 months from enrollment follow-up or upon progression, death or withdrawal from study participation, whichever occurs first. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Turn around Time (TAT) of cell free DNA (cfDNA) vs. tissue results | Turn around Time (TAT) of cell free DNA (cfDNA) vs. tissue results | From pre-treatment visit until month 12 or upon progression, whichever occurs first | 
| Time to treatment (TtT) initiation | Time to treatment (TtT) initiation | From the date of enrollment in the study until D1 (treatment initiation) | 
| Quantity not sufficient rate (QNS) of tissue | Quantity not sufficient rate (QNS) of tissue for clinically-actionable biomarker testing | From day 0 to pre-treatment visit | 
| Tissue Incomplete (TI) rate of tissue | Tissue Incomplete (TI) rate of tissue for National Cancer Center Network (NCCN) biomarker testing | From day 0 to pre-treatment visit | 
| Tumor Not Detected (TND) rate of cell free DNA (cfDNA) | Tumor Not Detected (TND) rate of cell free DNA (cfDNA) in blood | From pre-treatment visit until month 12 or upon progression, whichever occurs first | 
| Rescue rate of Quantity not sufficient (QNS) samples using cell free DNA (cfDNA)-derived genotyping | Rescue rate of Quantity not sufficient (QNS) samples using cell free DNA (cfDNA)-derived genotyping | From pre-treatment visit until month 12 or upon progression, whichever occurs first | 
| Rate response for patients that are actionable biomarker positive (either in cell DNA (cDNA) or tissue) treated with target-drugs | Rate response for patients that are actionable biomarker positive (either in cell DNA (cDNA) or tissue) treated with target-drugs according investigator criteria. | From visit 0 until month 12 or upon progression, whichever occurs first | 
| Rate of discovery of genomically mediated, acquired resistance to targeted therapies | Rate of discovery of genomically mediated, acquired resistance to targeted therapies in the biomarker-positive subsets. | From visit 0 until month 12 or upon progression, whichever occurs first |