Clinical trial NCT05520099: Observational Basket Trial to Collect Tissue to Train and Validate a Live Tumor Diagnostic Platform
Official title: Observational Basket Trial to Collect Tissue to Train and Validate a Live Tumor Diagnostic Platform (CYBRID-02)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Colorectal Cancer
Head and Neck Squamous Cell Carcinoma
Non Small Cell Lung Cancer
Cutaneous Melanoma
Endometrial Cancer
Urothelial Carcinoma
Clear Cell Renal Cell Carcinoma
Keywords: 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
Rectal Cancer
Endometrial Cancer
Forceps Biopsy
Metastatic solid tumor
Lead sponsor: Elephas
Sponsor class: INDUSTRY
Collaborators: name: Hoosier Cancer Research Network
First posted: 2022-08-29
Enrollment: 216
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects suspected or diagnosed with Stage III or IV:

* Bladder: Urothelial Carcinoma (UC)
* Kidney: Clear Cell Renal Cell Carcinoma (ccRCC)

Subjects suspected or diagnosed with Stage IV/metastatic:

* Colon and Rectum: MSI-High/dMMR Colorectal Cancer (CRC)
* Head and Neck: Squamous Cell Carcinoma (HNSCC), excluding nasopharyngeal and salivary gland cancers
* Lung: Non-small cell lung cancer (NSCLC)
* Skin: Cutaneous Melanoma, excluding Uveal Melanoma
* Uterus: endometrial cancer

Subjects suspected or diagnosed with:

* Any metastatic solid tumor with high TMB, MSI-High or dMMR and are being considered for treatment with ICI therapy.
* Any metastatic solid tumor that the clinician plans to treat with ICI therapy.

Brief summary: 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: 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.

Eligibility criteria: 1. 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.
2. Age ≥ 18 years at the time of consent.
3. Subjects must meet one of the following criteria:

   * Subjects suspected or diagnosed with Stage III or IV:

     * Bladder: Urothelial Carcinoma (UC)
     * Kidney: Clear Cell Renal Cell Carcinoma (ccRCC)
   * Subjects suspected or diagnosed with Stage IV/metastatic:

     * 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
     * Lung: Non-small cell lung cancer (NSCLC)
     * Skin: Cutaneous Melanoma, excluding Uveal Melanoma
     * Uterus: endometrial cancer
   * Subjects suspected or diagnosed with:

     * Any metastatic solid tumor with high TMB, MSI-High or dMMR and are being considered for treatment with ICI therapy.
     * Any metastatic solid tumor that the clinician plans to treat with ICI therapy. NOTE: This can be either in the setting of a trial, compassionate use, or the use of appropriate LDT tests that per clinician, render the patient eligible for ICI therapy, either frontline or a later line.
4. Subjects must be clinically able, at investigator discretion, to undergo additional core needle or forceps biopsy passes during their biopsy.
5. Subjects who are newly diagnosed or have suspected cancer must be treatment-naïve at the time of biopsy. All other subjects should have the biopsy performed before starting their next line of treatment.
6. Subjects with a newly confirmed 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.
7. Female subjects must not be pregnant.
8. Subjects with a known auto-immune disease that would render them ineligible for immune-oncology treatment are not eligible.
9. Immunocompromised subjects, and subjects known to be HIV positive and currently receiving antiretroviral therapy are not eligible. NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial.
10. Subjects who are enrolled or plan to be enrolled in a blinded oncology treatment trial are not eligible.

Primary outcomes:
measure: Sensitivity and Specificity of Cybrid Score for Predicting In-Vivo Clinical Response to Immune Checkpoint Inhibitors
timeFrame: 3 years
Secondary outcomes:
measure: 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)
timeFrame: 3 years
Other outcomes:
Locations:
city: Salinas
country: United States
facility: Salinas Valley Memorial Healthcare System
state: California
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Stuart
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Tampa
country: United States
facility: University of South Florida (Tampa General Hospital)
state: Florida
city: Louisville
country: United States
facility: University of Louisville James Graham Brown Cancer Center
state: Kentucky
city: Hagerstown
country: United States
facility: Meritus Center for Clinical Research
state: Maryland
city: Hagerstown
country: United States
facility: Meritus Health
state: Maryland
city: Hackensack
country: United States
facility: John Theurer Cancer Center
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: Elephas
name: Fred Hausheer, MD, FACP
role: STUDY_DIRECTOR
References:
citation: Chen S, Zhang Z, Zheng X, Tao H, Zhang S, Ma J, Liu Z, Wang J, Qian Y, Cui P, Huang D, Huang Z, Wu Z, Hu Y. Response Efficacy of PD-1 and PD-L1 Inhibitors in Clinical Trials: A Systematic Review and Meta-Analysis. Front Oncol. 2021 Apr 16;11:562315. doi: 10.3389/fonc.2021.562315. eCollection 2021.
citation: Cherukuri AR, Lubner MG, Zea R, Hinshaw JL, Lubner SJ, Matkowskyj KA, Foltz ML, Pickhardt PJ. Tissue sampling in the era of precision medicine: comparison of percutaneous biopsies performed for clinical trials or tumor genomics versus routine clinical care. Abdom Radiol (NY). 2019 Jun;44(6):2074-2080. doi: 10.1007/s00261-018-1702-1.