A Study to Evaluate the Impact of Liquid Biopsy in Participants With a Clinical Diagnosis of Advanced Cancer

Study Overview
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Brief Summary
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This is an international, prospective study to assess the impact of concomitant early use of liquid biopsy (FoundationOne® Liquid CDx) within the diagnostic pathway, compared with the standard of care diagnostic pathway, on the timing of routine cancer care in treatment-naïve participants presenting with a clinical diagnosis of advanced cancer, where the pathologic diagnosis has not yet been confirmed. Participants with one of the following two clinical presentations will be included: participants with evidence of de novo metastatic lung cancer or participants with evidence of de novo metastatic gastrointestinal cancer. Participants may have undergone different levels of diagnostic workup prior to enrollment. Participants who have not had tissue biopsy performed prior to enrollment will be classified as 'basic workup' and those who have had tissue biopsy performed prior to enrollment will be classified as 'extended workup'. During the diagnosis period, eligible participants will undergo liquid biopsy (FoundationOne® Liquid CDx assay; as per label) on blood samples. Blood samples will be tested using the FoundationOne® Liquid CDx assay at a central laboratory. In parallel, participants will undergo the standard of care diagnostic pathway, including tissue biopsy and histology workup, if not already done before enrollment, and molecular workup according to ESMO guidelines or national guidelines for each tumor type included in this study. Once a complete pathologic diagnosis has been made, the investigator (or multidisciplinary team) can complete an anti-cancer treatment recommendation assessment. Anti-cancer treatment recommendation should follow current practice and professional guidelines based on the results provided by either liquid biopsy (as per label) or tissue biopsy/standard of care.

Official Title
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An International Prospective Study to Evaluate the Impact of Liquid Biopsy in Participants With a Clinical Diagnosis of Advanced Cancer (L1ST)

Conditions
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Metastatic Lung Cancer, Metastatic Gastrointestinal Cancer

Intervention / Treatment
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* Diagnostic Test: FoundationOne® Liquid CDx Assay
* Diagnostic Test: Standard of Care Diagnostic Pathway


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants presenting with a clinical diagnosis of advanced cancer, falling into one of the following two clinical presentations: i) De novo metastatic lung cancer as evidenced by imaging demonstrating a lung nodule/mass and objective evidence of a metastatic process; OR, ii) De novo metastatic gastrointestinal cancer as evidenced by imaging demonstrating a metastatic process in the abdomen/pelvis Participants who are treatment naïve for the metastatic setting under study Ability to comply with the study protocol Participants must either: i) Have a tissue biopsy intended/planned to confirm malignant disease and histology; OR, ii) Have a tissue biopsy already performed but pathology has not yet been finalized. If a tissue biopsy has already been performed prior to ICF signature, then the subtyping of primary tumor may have already been assessed (i.e., for lung cancer TTF1, p40, and napsin A IHC staining may have already been performed). Exclusion Criteria: Participants deemed not fit for treatment with systemic therapy Participants deemed not fit for tissue biopsy Participants with hematological neoplasm Participants with primary malignant neoplasm of the brain Participants with any previous molecular testing (NGS or other methods) e.g., all immunohistochemistry staining recommended by ESMO aiming to define the treatment decision (i.e., for lung cancer ALK, EGFR, and PD-L1 IHC staining must not have already been performed). Participants in which tissue biopsy and primary histotyping have been performed can be included in the study. Prior treatment for metastatic cancer with the exception of participants who have already been diagnosed and treated for cancer, other than the cancer type under study, who have no evidence of relapse History of malignancy within 5 years prior to screening, with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival rate > 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer

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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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Basic Workup: Metastatic Lung Cancer Cohort<br>This cohort will enroll approximately 160 participants who have clinical evidence of de novo metastatic lung cancer and who have not had tissue biopsy performed prior to enrollment (classified as 'basic workup'). | Diagnostic Test: FoundationOne® Liquid CDx Assay<br>* Participants will undergo liquid biopsy (FoundationOne® Liquid CDx) on blood samples collected once they have a clinical diagnosis of advanced cancer (as per label). Blood samples will be tested using the FoundationOne® Liquid CDx assay at a central laboratory. Results of the FoundationOne® Liquid CDx assay will be provided to the investigator to be used in accordance with professional guidelines in oncology for patients with malignant neoplasms.<br>Diagnostic Test: Standard of Care Diagnostic Pathway<br>* Participants will undergo the local standard of care diagnostic pathway including tissue biopsy/standard of care (if tissue not available), pathology workup, and molecular workup, according to ESMO guidelines or national guidelines for each tumor type included in this study.<br>|
| Other: Basic Workup: Metastatic Gastrointestinal Cancer Cohort<br>This cohort will enroll approximately 160 participants who have clinical evidence of de novo metastatic gastrointestinal cancer and who have not had tissue biopsy performed prior to enrollment (classified as 'basic workup'). | Diagnostic Test: FoundationOne® Liquid CDx Assay<br>* Participants will undergo liquid biopsy (FoundationOne® Liquid CDx) on blood samples collected once they have a clinical diagnosis of advanced cancer (as per label). Blood samples will be tested using the FoundationOne® Liquid CDx assay at a central laboratory. Results of the FoundationOne® Liquid CDx assay will be provided to the investigator to be used in accordance with professional guidelines in oncology for patients with malignant neoplasms.<br>Diagnostic Test: Standard of Care Diagnostic Pathway<br>* Participants will undergo the local standard of care diagnostic pathway including tissue biopsy/standard of care (if tissue not available), pathology workup, and molecular workup, according to ESMO guidelines or national guidelines for each tumor type included in this study.<br>|
| Other: Extended Workup: Metastatic Lung Cancer Cohort<br>This cohort will enroll approximately 100 participants who have clinical evidence of de novo metastatic lung cancer and who have had tissue biopsy performed prior to enrollment (classified as 'extended workup'). | Diagnostic Test: FoundationOne® Liquid CDx Assay<br>* Participants will undergo liquid biopsy (FoundationOne® Liquid CDx) on blood samples collected once they have a clinical diagnosis of advanced cancer (as per label). Blood samples will be tested using the FoundationOne® Liquid CDx assay at a central laboratory. Results of the FoundationOne® Liquid CDx assay will be provided to the investigator to be used in accordance with professional guidelines in oncology for patients with malignant neoplasms.<br>Diagnostic Test: Standard of Care Diagnostic Pathway<br>* Participants will undergo the local standard of care diagnostic pathway including tissue biopsy/standard of care (if tissue not available), pathology workup, and molecular workup, according to ESMO guidelines or national guidelines for each tumor type included in this study.<br>|
| Other: Extended Workup: Metastatic Gastrointestinal Cancer Cohort<br>This cohort will enroll approximately 100 participants who have clinical evidence of de novo metastatic gastrointestinal cancer and who have had tissue biopsy performed prior to enrollment (classified as 'extended workup'). | Diagnostic Test: FoundationOne® Liquid CDx Assay<br>* Participants will undergo liquid biopsy (FoundationOne® Liquid CDx) on blood samples collected once they have a clinical diagnosis of advanced cancer (as per label). Blood samples will be tested using the FoundationOne® Liquid CDx assay at a central laboratory. Results of the FoundationOne® Liquid CDx assay will be provided to the investigator to be used in accordance with professional guidelines in oncology for patients with malignant neoplasms.<br>Diagnostic Test: Standard of Care Diagnostic Pathway<br>* Participants will undergo the local standard of care diagnostic pathway including tissue biopsy/standard of care (if tissue not available), pathology workup, and molecular workup, according to ESMO guidelines or national guidelines for each tumor type included in this study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Time to Diagnosis |  | From the date of first request for biopsy (tissue or blood) by a healthcare professional to the date of complete pathologic diagnosis (up to 12 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Time to Treatment Recommendation |  | From the date of first request for biopsy (tissue or blood) by a healthcare professional to the date of investigator's anticancer treatment recommendation (up to 12 weeks) | 
| Number of Molecular Testing Failures | Molecular testing failure is defined as cases in which the results of liquid biopsy or tissue biopsy/standard of care cannot be delivered to the treating physician. | Up to 12 weeks | 
| Percentage of Participants in Which Comprehensive Genomic Profiling (CGP) Led to a Molecularly Guided Treatment Option (MGTO) Recommendation | CGP refers to both the liquid biopsy and the standard of care diagnostic pathway. | Up to 12 weeks | 
| Percentage of Participants Diagnosed with an Actionable Driver Mutation Who Did Not Receive a MGTO Because Anticancer Treatment Needed to Begin Before the CGP Results Were Available |  | Up to 12 weeks | 
| Percentage of Participants With Concordant CGP Results Between the Liquid Biopsy and the Standard of Care Diagnostic Pathway on the Gene Alteration Level |  | Up to 12 weeks | 
| Percentage of Participants in Which Treatment Recommendation Based on Molecular Data from the Liquid Biopsy Were the Same as That Based on the Standard of Care Diagnostic Pathway |  | Up to 12 weeks | 
| Percentage of Participants in Which the MGTO Recommendation Issued Was Discordant Between the Liquid Biopsy Results and the Standard of Care Diagnostic Pathway Results |  | Up to 12 weeks | 
| Incidence and Severity of Liquid Biopsy Sample Collection-Related Adverse Events |  | Up to 17 weeks |