Observational Basket 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 across a basket of solid tumors, 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 checkpoint inhibitors (CPIs) 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 CPIs such as Pembrolizumab (Keytruda). These LTFs contain both tumor cells and infiltrating immune cells, which are critical in determining response to CPIs and other immunotherapies. In this observational clinical basket trial, participants will be recruited and their actual clinical response (using RECIST 1.1) to CPIs across five solid tumors (lung, head/neck, bladder, kidney, and skin) 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 CPIs like PDL1, MSI, and TMB.

Official Title
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Observational Basket Trial to Collect Tissue to Train and Validate a Live Tumor Diagnostic Platform (CYBRID-02)

Conditions
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Non Small Cell Lung Cancer, Melanoma, Kidney Cancer, Head and Neck Squamous Cell Carcinoma, Bladder Cancer, Colo-rectal Cancer, Endometrial 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. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. Age ≥ 18 years at the time of consent. Suspected or diagnosed with Stage IV/metastatic: Bladder: Urothelial Carcinoma (UC) Colon and Rectum: Microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) Colorectal Cancer (CRC) Head and Neck: Squamous Cell Carcinoma (HNSCC), excluding nasopharyngeal and salivary gland cancers Kidney: Clear Cell Renal Cell Carcinoma (ccRCC) Lung: Non-small cell lung cancer (NSCLC) Skin: Cutaneous Melanoma, excluding Uveal Melanoma Uterus: endometrial cancer Subjects must be clinically able, at investigator discretion, to undergo additional core needle biopsy passes during their biopsy from a tumor site that yields a biopsy of at least 10 mm in length. Subjects who are newly diagnosed or have suspected cancer must be treatment-naïve at the time of biopsy. Subjects 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. Subjects with a newly confirmed Stage IV diagnosis who have previously undergone a standard of care biopsy must be willing to undergo a separate biopsy procedure solely for the purposes of this study. This must be completed prior to receiving any anti-cancer therapy. Subjects who are receiving an investigational cancer treatment at time of registration are not eligible to participate in this study. Subjects with relapsing Stage IV cancer who are undergoing or plan to undergo a second line of treatment are not eligible. Female subjects must not be pregnant. Subjects with a known auto-immune disease that would render them ineligible for immune-oncology treatment are not eligible. Subjects with an immunocompromised state due to disease (e.g. HIV) or medication (e.g. transplant patients) 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 |
| --- | --- |
| Participants suspected of or diagnosed with Stage IV/metastatic cancer<br>Participants suspected of or diagnosed with Stage IV/metastatic: Colon and Rectum: MSI-H/dMMR CRC Uterus: endometrial cancer Lung: Non-small cell lung cancer (NSCLC) Head and Neck: Squamous Cell Carcinoma (HNSCC), excluding nasopharyngeal and salivary gland cancers Kidney: Clear Cell Renal Cell Carcinoma (ccRCC) Bladder: Urothelial Carcinoma (UC) Skin: Cutaneous Melanoma, excluding Uveal Melanoma | Procedure: Core needle biopsy<br>* Additional core needle biopsy (CNB) passes 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. For (suspected) NSCLC patients, an extra CNB will only be taken through metastatic sites amenable to a secondary pass (e.g. liver or lymph node metastases), not through the primary lung tumor to prevent potential complications. An optional peripheral blood collection will be performed on the same day as the biopsy procedure occurs, ideally prior to the biopsy. 10 mL of blood will be collected.<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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Rectal Cancer, Endometrial Cancer, Core Needle Biopsy, Live tumor fragments, Immunotherapy, Immunotherapy prediction, 3D culture, Ex vivo platform, Immune checkpoint inhibitors, Non Small Cell Lung Cancer, NSCLC, Head and Neck Squamous Cell Carcinoma, HNSCC, Clear Cell Renal Cell Carcinoma, ccRCC, Urothelial Carcinoma, Melanoma, Colon Cancer