SIBYL: obServation of Therapy Response With lIquid BiopsY evaLuation

Study Overview
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Brief Summary
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The purpose of SIBYL is to generate clinical validity data for the ability of a future version of Guardant360 developed by Guardant Health to measure response to systemic therapy in patients with unresectable advanced solid tumors. It is necessary to collect clinical data points and treatment outcomes in order to demonstrate clinical validity for longitudinal monitoring with ctDNA and correlation of ctDNA dynamics with therapeutic response, as evaluated by standard methods, including RECIST 1.1 and CT scan measurements.

Official Title
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SIBYL: obServation of Therapy Response With lIquid BiopsY evaLuation

Conditions
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Breast Cancer, Non-small Cell Lung Cancer, Colorectal Cancer

Intervention / Treatment
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* Diagnostic Test: Guardant360


Participation Criteria
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Eligibility Criteria
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Will be treated with a first- or second-line systemic and/or oral standard of care regimen at the enrolling site Patient is either treatment naive and has not yet commenced first line SOC therapy OR patient has completed a prior line of SOC therapy and will commence subsequent line of SOC therapy Provide written informed consent to participate in the study Diagnosed with an unresectable advanced solid malignancy and have a histologically confirmed cancer that qualifies for inclusion, defined as: Non-small cell lung cancer (stage III-IV) Colorectal adenocarcinoma (stage III-IV) Breast Cancer (stage III-IV) Exclusion Criteria: History of a prior solid or hematological malignancy within 5 years of enrollment Life expectancy < 12 weeks Unable to collect baseline blood sample prior to starting SOC regimen Is participating in an interventional clinical trial or another observational study that is evaluating the performance of another genomic test for detecting/predicting clinical response/progression

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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort 1: Unresectable Stage III/IV NSCLC<br>Blood samples collected will be banked | Diagnostic Test: Guardant360<br>* Guardant360 is a qualitative next generation sequencing (NGS)-based in vitro diagnostic device for detection of single nucleotide variants (SNVs), insertions and deletions (indels), copy number amplifications (CNAs), and fusions in genes frequently mutated in cancer, using circulating cell-free DNA (cfDNA) obtained from the plasma of peripheral whole blood collected in Streck Cell-Free DNA Blood Collection Tubes.<br>|
| Cohort 2: Stage IV Colorectal<br>Blood samples collected will be banked | Diagnostic Test: Guardant360<br>* Guardant360 is a qualitative next generation sequencing (NGS)-based in vitro diagnostic device for detection of single nucleotide variants (SNVs), insertions and deletions (indels), copy number amplifications (CNAs), and fusions in genes frequently mutated in cancer, using circulating cell-free DNA (cfDNA) obtained from the plasma of peripheral whole blood collected in Streck Cell-Free DNA Blood Collection Tubes.<br>|
| Cohort 3: Unresectable Stage III/IV Breast - HR+ HER2-<br>Blood samples collected will be banked | Diagnostic Test: Guardant360<br>* Guardant360 is a qualitative next generation sequencing (NGS)-based in vitro diagnostic device for detection of single nucleotide variants (SNVs), insertions and deletions (indels), copy number amplifications (CNAs), and fusions in genes frequently mutated in cancer, using circulating cell-free DNA (cfDNA) obtained from the plasma of peripheral whole blood collected in Streck Cell-Free DNA Blood Collection Tubes.<br>|
| Cohort 4: Unresectable Stage III/IV Breast - HR- HER2+<br>Blood samples collected will be banked | Diagnostic Test: Guardant360<br>* Guardant360 is a qualitative next generation sequencing (NGS)-based in vitro diagnostic device for detection of single nucleotide variants (SNVs), insertions and deletions (indels), copy number amplifications (CNAs), and fusions in genes frequently mutated in cancer, using circulating cell-free DNA (cfDNA) obtained from the plasma of peripheral whole blood collected in Streck Cell-Free DNA Blood Collection Tubes.<br>|
| Cohort 5: Unresectable Stage III/IV Breast - Triple Positive<br>Blood samples collected will be banked | Diagnostic Test: Guardant360<br>* Guardant360 is a qualitative next generation sequencing (NGS)-based in vitro diagnostic device for detection of single nucleotide variants (SNVs), insertions and deletions (indels), copy number amplifications (CNAs), and fusions in genes frequently mutated in cancer, using circulating cell-free DNA (cfDNA) obtained from the plasma of peripheral whole blood collected in Streck Cell-Free DNA Blood Collection Tubes.<br>|
| Cohort 6: Unresectable Stage III/IV Breast - Triple Negative<br>Blood samples collected will be banked | Diagnostic Test: Guardant360<br>* Guardant360 is a qualitative next generation sequencing (NGS)-based in vitro diagnostic device for detection of single nucleotide variants (SNVs), insertions and deletions (indels), copy number amplifications (CNAs), and fusions in genes frequently mutated in cancer, using circulating cell-free DNA (cfDNA) obtained from the plasma of peripheral whole blood collected in Streck Cell-Free DNA Blood Collection Tubes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of ctDNA to Detect Disease Progression | The Primary Endpoint, sensitivity of ctDNA to detect disease progression, will be evaluated from all eligible subjects within the primary study cohorts (breast cancer, NSCLC, or CRC) | 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RECIST Response | RECIST v1.1 response: defined as the tumor response to treatment as measured by restaging scans in subjects who have increasing or decreasing ctDNA quantities before the time of scan and correlating this change with the clinical response | 6 years | 
| Progression-Free Survival (PFS) | PFS: defined as the quantitative changes in ctDNA that correlate or associate with participant's progression free survival on each line of SOC therapy | 6 years | 
| Lead Time | Lead time: defined as the interval between ctDNA detection or increase and clinical detection of disease progression | 6 years |