SIBYL: obServation of Therapy Response With lIquid BiopsY evaLuation

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.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Colorectal Cancer; Non-small Cell Lung Cancer
• Intervention / Treatment: Diagnostic test: Guardant360

• Study Type: Observational
• Enrollment (Estimated): 470

Contacts and Locations

• Study Contact: Name: Clinical Trial Operations; Phone Number: 8556988887; Email: sibyl@guardanthealth.com

Study Locations

• United States
  • Illinois
    • Skokie, Illinois, United States, 60077-1384
      • Recruiting
      • Orchard Healthcare Research Inc.
      • Contact: Ira Oliff

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The primary study population will include participants with Non-small cell lung cancer (stage III-IV), Colorectal adenocarcinoma (stage III-IV), and Breast Cancer (stage III-IV), as per inclusion/exclusion criteria. Approximately 470 total patients will be enrolled into the study.

Description

Inclusion Criteria

Each participant must satisfy all the following criteria to be enrolled in the study:

1. Age ≥18 years old
2. Are treated with systemic therapy and/or oral SOC regimen at the site of enrollment during entirety of study
3. Patient is either treatment naive and has not yet commenced first line SOC therapy OR patient has completed first line SOC therapy and will commence second line of SOC therapy
4. Able to understand, and capable of providing written consent to participate in the study
5. Are willing to have de-identified clinical data shared with investigators at regular intervals outlined in the study protocol and informed consent
6. Are willing to provide blood samples at enrollment and at subsequent clinical visits

7. Have a histologically confirmed Index cancer that qualifies for inclusion, defined as:

   • Cohort 1: Unresectable Stage III/IV NSCLC (~125)
   • Cohort 2: Stage IV Colorectal (~125)
   • Cohort 3: Unresectable Stage III/IV Breast - HR+ HER2- (~55)
   • Cohort 4: Unresectable Stage III/IV Breast - HR- HER2+ (~55)
   • Cohort 5: Unresectable Stage III/IV Breast - HR+ HER2+ (~55)
   • Cohort 6: Unresectable Stage III/IV Breast - Triple Negative (~55) Determination of stage for eligibility assessment and enrollment should be based on clinical or pathologic stage.

Exclusion Criteria

Any potential participant who meets and of the following criteria at the time of initial enrollment will be excluded from participating in the study:

1. History of prior solid malignancy or hematological malignancy within five years of enrollment
2. Life expectancy ≤12 weeks
3. Unable to collect a baseline blood sample during a SOC venipuncture, and prior to starting SOC regimen
4. Is participating in a clinical trial or another observational study that is evaluating the performance of another genomic test for detecting/predicting clinical response/progression

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1: Unresectable Stage III/IV NSCLC; Blood samples collected will be banked	Diagnostic test: Guardant360; 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.
Cohort 2: Stage IV Colorectal; Blood samples collected will be banked	Diagnostic test: Guardant360; 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.
Cohort 3: Unresectable Stage III/IV Breast - HR+ HER2-; Blood samples collected will be banked	Diagnostic test: Guardant360; 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.
Cohort 4: Unresectable Stage III/IV Breast - HR- HER2+; Blood samples collected will be banked	Diagnostic test: Guardant360; 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.
Cohort 6: Unresectable Stage III/IV Breast - Triple Negative; Blood samples collected will be banked	Diagnostic test: Guardant360; 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.
Cohort 5: Unresectable Stage III/IV Breast - HR+ HER2+; Blood samples collected will be banked	Diagnostic test: Guardant360; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Guardant Health, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2023
• Primary Completion (Estimated): December 30, 2030
• Study Completion (Estimated): December 30, 2030

Study Registration Dates

• First Submitted: June 29, 2023
• First Submitted That Met QC Criteria: June 29, 2023
• First Posted (Actual): July 7, 2023

Study Record Updates

• Last Update Posted (Actual): August 22, 2025
• Last Update Submitted That Met QC Criteria: August 18, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: 06-MX-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No