SIBYL: obServation of Therapy Response With lIquid BiopsY evaLuation

September 8, 2026 updated by: Guardant Health, Inc.
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

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

470

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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
Time Frame: 6 years
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
Time Frame: 6 years
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)
Time Frame: 6 years
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
Time Frame: 6 years
Lead time: defined as the interval between ctDNA detection or increase and clinical detection of disease progression
6 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Guardant Health, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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)

September 11, 2026

Last Update Submitted That Met QC Criteria

September 8, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 06-MX-001

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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