Observational Lung Trial to Collect Tissue to Train and Validate a Live Tumor Diagnostic Platform

Study Overview
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Brief Summary
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The primary objective of this study is to determine the ex-vivo prognostic accuracy of the Cybrid live tumor diagnostic platform using in-vivo RECIST 1.1 as the reference method.

Detailed Description
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Cancer is a leading cause of death and despite many new drugs, a major diagnostic challenge remains knowing which drug will work best for a patient. A new class of drugs called immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, current diagnostic methods (e.g. PDL1, MSI and TMB) do not accurately predict which patients will respond. Elephas is developing a diagnostic platform using small 3D Live Tumor Fragments (LTFs) from participants for accurate prediction of drug response with a focus on ICIs such as Pembrolizumab (Keytruda). These LTFs contain both tumor cells and infiltrating immune cells, which are critical in determining response to ICIs and other immunotherapies. In this observational clinical trial, 200 Non-Small Cell Lung Cancer (NSCLC) participants will be recruited and their actual clinical response to ICIs (using RECIST 1.1) will be compared to the platform's predictive Artificial Intelligence (AI) score that is based on RNA, clinical data, and 3D microscopy images. The sensitivity and specificity of the platform's score will be determined and compared to current diagnostic methods for ICIs like PDL1, MSI, and TMB.

Official Title
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Observational Lung Trial to Collect Tissue to Train and Validate a Live Tumor Diagnostic Platform (CYBRID-01)

Conditions
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Non Small Cell Lung Cancer, Metastatic Non Small Cell Lung Cancer, NSCLC, Metastatic NSCLC - Non-Small Cell Lung Cancer

Intervention / Treatment
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* Procedure: Core needle biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent and HIPAA authorization for release of personal health information prior to registration. Age ≥ 18 years at the time of consent. Suspected of or diagnosed with Stage IV/metastatic non-small cell lung cancer (NSCLC). Must be clinically able, at investigator discretion, to undergo additional core needle biopsy passes (up to four) during their biopsy from a tumor site that yields a biopsy of at least 10 mm in length. These additional core needle biopsies will be collected from a metastatic site amenable to additional passes (e.g. liver or lymph nodes). Core needle biopsy passes may also be collected from the primary tumor site (lung) if it can be accessed at no risk of pneumothorax (e.g., large, lateral tumor), and the site is amenable to additional passes per the clinical investigator. Participants who are newly diagnosed or have suspected cancer must be treatment-naïve at the time of biopsy Participants who are Stage I, II, or III and have progressed to Stage IV/metastatic cannot have received any anti-cancer treatment for at least 2 months prior to biopsy. Exclusion Criteria: Any Lung cancer patient for whom an extra biopsy might pose a clinical risk, either due to not having liver, lymph node metastases or for any other reason. Any (mental) impairment that would render the participant unable to understand his/her participation in the study. Auto-immune disease that would render them ineligible for immune-oncology treatment. Immunocompromised state due to disease (e.g., HIV) or medication (e.g., transplant). Participants who are receiving an investigational cancer treatment at time of enrollment Participants who are pregnant are not eligible. Participants with relapsing Stage IV lung cancer who are undergoing or plan to undergo a second line of treatment are not eligible.

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 |
| --- | --- |
| Stage IV or metastatic Non Small Cell Lung Cancer (NSCLC)<br>Participants who are undiagnosed, have undergone imaging, and are suspected to have Stage IV lung cancer with a primary tumor or metastatic sites amenable to additional core needle biopsy passes; also, participants with stage I,II, or III diagnosis of NSCLC who are being re-biopsied after imaging-confirmed progression to metastatic disease, with a primary tumor or metastatic sites amenable to additional core needle biopsy passes; also, participants who have a confirmed diagnosis of NSCLC who have undergone a SOC biopsy procedure and will undergo a separate procedure for the purposes of this study. | Procedure: Core needle biopsy<br>* Additional core needle biopsy (CNB) passes from either the primary lung or a metastatic site will be obtained for tumors amenable to an additional pass that are at least 10 mm in length. If a 16 gauge needle is used for collection, a minimum of 1 additional core needle biopsy pass must be taken. If an 18 gauge needle is used, a minimum of 2 additional passes must be taken. Up to 4 additional passes may be taken with either gauge size for this study as deemed amenable by the clinician.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity and Specificity of Cybrid Score for Predicting In-Vivo Clinical Response to Immune Checkpoint Inhibitors | The ex-vivo prognostic accuracy of the Cybrid live tumor diagnostic platform will be determined using in-vivo RECIST 1.1 as the reference method. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the Area Under the Receiver Operating Characteristic Curve (AUC) of Cybrid Score and Compare to the AUCs of Current FDA Approved Predictive Biomarkers PD-L1 and Tumor Mutation Burden (TMB) | The AUC of Cybrid Score will be established with a clinically meaningful confidence interval and compared to the AUCs of established FDA approved biomarkers for predicting clinical response to ICIs. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic NSCLC, NSCLC, Non Small Cell Lung Cancer, Core needle biopsy, Live tumor fragments, Immunotherapy, Immunotherapy prediction, 3D culture, Ex vivo platform, Immune checkpoint inhibitors